J Oral Maxillofac Surg

68:2207-2220, 2010

Corticosteroid Administration in Oral and

Orthognathic Surgery: A Systematic
Review of the Literature
and Meta-Analysis
Anne E.B. Dan, DDS,* Torben H. Thygesen, DDS, PhD,† and
Else M. Pinholt, DDS, MSc, DrOdont‡

Purpose: This study evaluated the effect of corticosteroid (CS) administration on edema, analgesia, and
neuroregeneration in conjunction with surgical dental extraction, orthognathic surgery, and the risk of
developing side effects.
Materials and Methods: A systematic search of the literature was made. The primary predictor
variable was CS administration and the outcome variables were edema, pain, and infection. A
meta-analysis was performed. The risk of other side effects was evaluated through a simple review.
Results: In oral surgery, most clinical trials showed a significant decrease in edema (P ⬍ .0001) after
CS, and local injection of methylprednisolone ⱖ25 mg was expected to result in a significant decrease
in edema. Regarding the analgesic effect, several clinical trials showed a decrease in pain after CS (P ⬍
.0001). Further, CS administration resulted in a slightly higher risk of infection (relative risk, 1.0041), but
with a P value of .89. CS could be administered with no increased risk of infection. In orthognathic
surgery, methylprednisolone ⱖ85 mg administered intravenously seemed sufficient to produce a signif-
icant decrease in edema, and several trials pointed toward a neuroregeneration effect, but no statistical
analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of
chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteone-
crosis, steroid-induced psychosis, and adrenal suppression was seen. There were no reports of decreased
healing.
Conclusion: These findings suggest that the administration of CS in oral surgery decreases edema
and pain significantly, with no higher risk of infection and with a minimum risk of other side effects.
© 2010 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 68:2207-2220, 2010

In the late 1960s and early 1970s, corticosteroid (CS)
administration was advocated in conjunction with
various oral surgical interventions to minimize edema
and possibly decrease pain and promote neuroregen-
eration.1,2
The most commonly administered types of CS
are betamethasone, dexamethasone, and methyl-
prednisolone, administered intravenously, orally or
by injection into the masseter muscle.1
The administration of CS is thought to inhibit mast
cell production and secretion of cytokine, kinin, and
histamine.3-5 This should promote an inhibition of
thromboxane6,7 and bradykinin,8 resulting in less blood
vessel dilatation and less permeability.

*Research Assistant, Department of Oral and Maxillofacial Sur-
gery, School of Dentistry, Faculty of Health Sciences, University of
Copenhagen, Copenhagen, Denmark.
†Chief Surgeon, Associate Professor, Department of Oral and
Maxillofacial Surgery, K. Odense University Hospital, Odense, Den-
mark.
‡Professor and Head, Department of Oral and Maxillofacial Sur-
gery, School of Dentistry, Faculty of Health Sciences, University of
Copenhagen, Copenhagen, Denmark.
Address correspondence and reprint requests to Dr Dan:
Department of Oral and Maxillofacial Surgery, Institute of Odontol-
ogy, Faculty of Health Science, University of Copenhagen, Bleg-
damsvej 3B, 2200 Copenhagen N, Seeland, Denmark; e-mail:
dan_anne@hotmail.com
© 2010 American Association of Oral and Maxillofacial Surgeons
0278-2391/10/6809-0027$36.00/0
doi:10.1016/j.joms.2010.04.019

2207
2208
Another edema-decreasing factor, which has
been claimed to be the result of CS administration,
is the inhibition of lysozyme-induced membrane
rupture, which decreases the local release of pro-
teolytic enzymes and hyaluronidase.9
Furthermore, the administration of CS is thought to
promote an inhibition of the synthesis of prostaglan-
din, thereby facilitating an analgesic effect.10,11
Nerve damage is the result of direct or indirect
injury to the nerves. Compression or trauma results in
edema in nearby tissues or release of inflammatory
mediators that temporarily irritate the nerves.12 Some
investigators have suggested that CS promotes the
healing of nerves.12,13
However, CS administration has been discouraged
because of the fear of serious side effects,14-16 such as
avascular osteonecrosis,17-24 adrenal suppression,25-30
decreased healing potential, a higher infection
rate,30-35 and steroid-induced psychosis.14,36-44
It has been stated that the exogenic CS has a neg-
ative feedback effect on the hypothalamus-pituitary-
adrenal axis, resulting in suppression of the normal
endogenic secretion of cortisol. The suppression
reaches its maximum on the third day and normalizes
on the seventh day, which seems to be of little or no
significance in the postoperative period, and prob-
lems only occur when this temporary suppression
turns into a chronic state of adrenal suppres-
sion.28,45-49
In animals, the administration of CS can produce
changes in hippocampal structure and function.36 In
humans, it results in euphoria37-39 or, more rarely, in
suicidal thoughts due to a lowering of serotonin levels
in the brain.40
Post-traumatic avascular osteonecrosis primarily in
the femur is seen because of various medical conditions
and after treatment with high-dose (long-duration) pred-
nisolone, all of which inhibit microvascularity in bone
and thereby cause ischemia and necrosis.30,50
Table 1. EQUIVALENT DOSE WITH REGARD TO ANTI-INFLAMMATORY EFFECT
Type* Anti-Inflammatory Potency
Cortisol 1 8-12
Prednisolone 3-5
Methylprednisolone 3-5
Triamcinolone 3-5
Paramethasone 10
Betamethasone 20-30
Dexamethasone 20-30
*Equivalent volumes of cortisol, prednisolone, methylprednisolone, triamcinolone, paramethasone, betamethasone, and
dexamethasone are listed with regard to anti-inflammatory effects and respective values of anti-inflammatory potency and
half-time.9,79 It should be noted that available studies using orally administered dexamethasone were recalculated according
to bioavailability, to a further decrease of 20%.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.
CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY
Theoretically, the administration of CSs should in-
hibit fibroblast function and contribute to a decrease
in the rate of healing and an increase in the rate of
infection.30-32
Does edema actually require prophylactic CS treat-
ment? Rarely, edema can be life-threatening if it re-
sults in airway obstruction, but this is the case only in
orthognathic surgery, severe trauma in general, and
major head and neck surgery.51 In oral surgery, indi-
cations for the use of prophylactic CS are functional
and esthetic.
The purpose of this review and meta-analysis of
clinical trials (on the topic of CS use in oral and
orthognathic surgery) was to clarify whether CS
administration does indeed significantly decrease
edema and pain and promote neuroregeneration.
Furthermore, we wanted to identify the minimum
effective dose of CS in relation to onset, duration,
and route of administration. In addition, we evalu-
ated whether CS administration did in fact intro-
duce an increased risk of side effects.
Materials and Methods
Articles were located through PubMed (www.
pubmed.org) and the Cochrane Database (www.
cochrane.org) using the search words corticoste-
roid ⫹ oral surgery/orthognathic surgery ⫹ neu-
roregeneration/avascular osteonecrosis/steroid-
induced psychosis/healing/infection.
The articles were evaluated on the presence or
absence of the following parameters:
● Introduction: A clear hypothesis and aim of the study
and the correct use and citation of prior studies.
● Method: A logical coherence between the aim of
the trial and the choice of method, sufficient num-
ber of patients to provide statistical strength, use of
Equivalent Dose With Regard
Half-Life in Hours to Anti-Inflammatory Effect
20 mg
12-36 5 mg
12-36 4 mg
12-36 4 mg
2 mg
36-54 0.6 mg
36-54 0.75 mg
DAN, THYGESEN, AND PINHOLT 2209

Abbreviations: IM, intramuscular; IV, intravenous; mand, mandibular teeth surgically removed; max, maxillary teeth surgically removed; NS, not significant; postop,

NOTE. Table lists trials in which corticosteroids were administered to evaluate postoperative edema. All studies were randomized, double-blind studies tested against placebo
control groups, validity, precision, reliability of the

P Value

.0003
⬍.001

⬍.005

⬍.001
⬍.056
.001

.006

⬍.001
⬍.001
NS
⬍.05

⬍.05
measurement method, and repeatability of the trial.
● Results and discussion: Coherence between pre-
sented results and hypothesis, well-presented

Preop ⫹ postop
Time of Steroid
findings, well-documented conclusions, and no

Delivery
presence of bias.

Postop
Postop

Postop
Preop
Preop
Preop

Preop
Preop
Preop
Preop
Preop
The administered doses of CS in the selected
articles were recalculated to equivalent anti-inflam-

Submucosal injection
Method of Delivery
matory doses of methylprednisolone, to facilitate
comparison (betamethasone 9 mg ⫽ [9 mg/0.6 mg] ⫻

(saline). P values greater than .05 indicate no significant decrease in edema; P values less than .05 indicate a significant decrease in edema.
4 ⫽ methylprednisolone 60 mg). Further, the doses of
orally administered dexamethasone were decreased

Oral

Oral
by 20% to adjust the dose according to the bioavail-

IM

IM

IM

IM
IV
IV

IV

IV
IV
ability difference between oral and intravenous ad-
ministration and local injection (Table 1).

Dose (mg)
Original
Regarding CS administration and decreased edema

125
9
125

25
4
6
9
8
40
4
20
4
in oral surgery, 20 articles2,3,49,52-68 were found, and

Table 2. SELECTED ARTICLES IN ORAL SURGERY (CORTICOSTEROID ADMINISTRATION AND EDEMA DECREASE)
82,3,55,64-68 were rejected due to the lack of objective
parameters,66 lack of statistical analysis,2,68 not being

sodium succinate
Methylprednisolone
Methylprednisolone

Methylprednisolone

Methylprednisolone
Original Steroid
double-blinded64,65 or randomized,65 and use of insuf-

Dexamethasone
Dexamethasone

Dexamethasone

Dexamethasone

Dexamethasone
Betamethasone

Betamethasone
ficient evaluation methods (Table 2).3,55 The remain-

Prednisolone
ing 12 articles49,52,53,56-63,69 showed great diversity
regarding the dose, route of administration, and drug
of choice. Of the 12 selected articles, only 652,53,56-59

Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.
provided sufficient data to be included in the meta-
Age (yr)

18-24
Mean

22.8
23.4
analysis.
24
26
22

23
24
18
23

22
24
On the topic of CS administration and decreased pain in
oral surgery, 13 articles were found,2,49,52,53,56,58-62,63,67,69
Subjects
Control

and 2 were excluded because of lack of statistical analy-

24
24
20

15
43
25
12
25
20
30
11
60
sis,2,67 leaving 11 articles49,52,53,56,58-62,63,69 to be included
in the review (Table 3). Of these 11 articles, only 5 arti-
cles52,53,56,59,63 provided sufficient data to be included in
Subjects Using
Steroids

the meta-analysis.
24
24
20

15
43
25
12
25
20
30
11
60

Regarding orthognathic surgery, 5 eligible trials were

found1,4,70-72; 2 were rejected due to lack of randomiza-
tion and blinding.1,4 The remaining 3 trials were in-
cluded in the review and no meta-analysis could be
Max/mand
Max/mand

Max/mand
Max/mand
Max/mand

Max/mand
Max/mand
Jaw Arch

performed on decreased edema after orthognathic sur-

Mand

Mand
Mand

Mand
Mand

gery due to insufficient available data (Table 4).

Eleven articles2,3,49,52,53,57-60,63,69 on infection rate
Controlled Trial

after oral surgery were available; 2 were excluded due

Randomized-

to lack of statistical analysis2 and insufficient evalua-

Yes
Yes
Yes

Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

tion method used.3 The remaining 9 arti-

postoperative; preop, preoperative.

cles49,52,53,57-60,63,69 were included in the review (Ta-

ble 5). Of these 9 articles,49,52,53,57-60,63,69 all provided
sufficient data to be included in the meta-analysis.
Schmelseizen and Frölich,60 1989

Because of the lack of sufficient numbers of avail-

Skjelbred and Løkken,52 1982

Skjelbred and Løkken,53 1982

Beirne and Hollander,56 1986

able double-blinded and randomized studies, other CS

Buyukkurt et al,61 2006

Baxendale et al,59 1993

effects such as neuroregeneration and the risk of side

Neupert et al,63 1992
Graziani et al,62 2006
Study

Milles et al,58 1993

effects (avascular osteonecrosis, steroid-induced psy-

Esen et al,49 1999

Pedersen,69 1985
Holland,57 1987

chosis, adrenal suppression, and decreased healing)

could be reviewed only by including randomized,
controlled trials and single-case studies. No meta-anal-
ysis was performed and, hence, no valid conclusion
2210 CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY

Table 3. SELECTED ARTICLES IN ORAL SURGERY (CORTICOSTEROID ADMINISTRATION AND ANALGESIA)

Randomized- Subjects Mean Original Analgesic

Controlled Using Control Age Original Steroid Dose Method of Time of Steroid Effect (P
Study Trial Jaw Arch Steroids Subjects (yr) Used (mg) Delivery Delivery Value)

Skjelbred and Yes Max/mand 24 24 24 Betamethasone 9 IM Preop ⬍.001

Løkken,52 1982
Beirne and Yes Max/mand 24 24 26 Methylprednisolone 125 IV Preop ⬍.01
Hollander,56 1986
Esen et al,49 1999 Yes Mand 20 20 22 Methylprednisolone 125 IV Preop ⬍.0001
sodium succinate
62
Graziani et al, 2006 Yes Mand 15 43 24 Dexamethasone 21.3 Submucosal Postop .02
injection
Schmelseizen and Yes Max/mand 25 25 18 Dexamethasone 6 Oral Preop ⫹ postop .01
Frölich,60 1989
Skjelbred and Yes Max/mand 24 24 24 Betamethasone 9 IM Postop ⬎.1
Løkken,53 1982B
Baxendale et al,59 Yes Max/mand 25 25 22.8 Dexamethasone 8 Oral Preop ⬍.005
1993
Pedersen,69 1985 Yes Mand 30 30 22 Dexamethasone 4 IM Preop ⬎.05
Buyukkurt et al,61 Yes Mand 15 15 23 Prednisolone 25 IM Postop ⬎.05
2006
Milles et al,58 1993 Yes Max/mand 11 11 24 Methylprednisolone 20 IV Preop ⬎.05
Neupert et al,63 1992 Yes Max/mand 60 60 NA Dexamethasone 21.3 IV Preop ⬍.0001

Abbreviations: IM, intramuscular; IV, intravenous; mand, mandibular teeth surgically removed; max, maxillary teeth surgically
removed; NA, no available data; postop, postoperative; preop, preoperative.
NOTE. Table lists trials in which corticosteroids were administered to evaluate postoperative analgesia. All studies were
randomized, double-blind studies tested against placebo (saline). P values greater than .05 indicate no significant decrease in
postoperative pain; P values less than .05 indicate significant decreases in postoperative pain.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.

can be made. This section of the report should serve
only as a basic guideline for further investigation.
Meta-analysis was performed on data in oral surgery
and evaluated CS compared with placebo, resulting in
edema/no edema, analgesia/no analgesia, and infec-
tion/no infection.
The meta-analysis was performed using an inverse
variance method, and results were summarized using
forest plots73 and relative risks (RRs), estimated based
on fixed and random effects models.74
Heterogeneity was quantified (␶2, H[ ; ], I2 [% , %])
and tested (Q value, degrees of freedom, P value); and
in the Results section, RR with 95% confidence inter-
val, P value; and Z value are given.74
Further, a forest plot was done for oral surgical
edema, analgesia, and infection rate using a logarithmic
scale for RR to achieve symmetrical confidence inter-
vals.73
Results
CORTICOSTEROID ADMINISTRATION IN
ORAL SURGERY
Edema
Five reviews on oral surgery and CS administration
were available. The reviews concluded that CS is
effective in decreasing edema and thus should be
administered, although different dosages, administra-
tion routes, times of onset, and durations of treat-
ments were used.37-39,51,75
In oral surgery, 12 trials49,52,53,56-63,69 were selected,
in which CSs were administered before, during, or after
surgical extraction, and these were divided into 2
groups. In group 1, 11 studies reported significantly
decreased edema because of CS administration at vari-
ous times and doses.49,52,53,56-62,69 In group 2, 1 trial by
Neupert et al63 did not report decreased edema after CS
administration. The reasons Neupert et al did not report
significantly decreased edema were probably due to a
lack of sensitivity in the method used to measure edema,
the possibility that the dose was close to the minimum
dose threshold, and in the choice of route of adminis-
tration. These possibilities are supported by the finding
by Pedersen69 of significantly decreased edema when
administering the same dose at the same time and dura-
tion as Neupert et al, but by injection into the masseter
muscle.
Figure 1A shows that most trials resulted in signifi-
cantly decreased edema after administration of CSs. Ad-
ministration had effect when administered in various
combinations of dose and time of onset, route, and
duration of treatment. Based on Figure 1A, the single
threshold dose is expected to be methylprednisolone 0
to 25 mg, but this should be verified through further
clinical trials.
A forest plot of the selected 6 studies52,53,56-59 was
made. Figure 1B shows the results of 6 randomized
clinical trials combined in a collaborative meta-analysis
of 232 M3 surgery sites treated with CS or placebo and
the composite endpoint being moderate/severe edema
 DAN, THYGESEN, AND PINHOLT
Table 4. SELECTED ARTICLES IN ORTHOGNATHIC SURGERY (CORTICOSTEROID ADMINISTRATION AND EDEMA DECREASE)

Randomized- Subjects Mean

Controlled Using Control Age Original Type of Method of Time of Steroid
Study Trial Design Type Steroids Subjects (yr) Steroid Used Original Dose Delivery Delivery P Value

Weber and Griffin,70 1994 Yes Sagittal split osteotomy 8 4 NA Dexamethasone 16 mg preop IV Preop ⬍.05
Weber and Griffin,70 1994 Yes Sagittal split osteotomy 8 4 NA Dexamethasone 16 mg preop ⫹ IV Preop ⫹ postop ⬍.05
8 mg ⫻ 3
postop
Peillon et al,71 1996 Yes Le Fort I 16 16 NA Methylprednisolone 1.5 mg/kg IV Preop ⫹ postop NA
Munro et al,72 1986 Yes Le Fort I/II, 17 19 15 Dexamethasone 0.5 mg/kg preop IV Preop ⫹ postop ⬎.05
hemimandibulectomy, and 0.25 mg/
and sagittal split kg for 48 h
mandibular osteotomy
Abbreviations: IM, intramuscular; IV, intravenous; mand, mandibular teeth surgically removed; max, maxillary teeth surgically removed; NA, no available data; postop,
postoperative; preop, preoperative.
NOTE. Table lists trials in which corticosteroids were administered to evaluate postoperative edema. All studies were randomized, double-blind studies tested against placebo
(saline). P values greater than .05 indicate no significant decrease in postoperative edema; P values less than .05 indicate significant decreases in postoperative edema.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.

Table 5. SELECTED ARTICLES IN ORAL SURGERY (CORTICOSTEROID ADMINISTRATION AND INFECTION)

Subjects
Randomized- Infections Subjects Infections in in Mean Original Method
Controlled in CS in CS Control Control Age Original Steroid Dose of Time of Steroid
Study Trial Jaw Arch Group Group Group Group (yr) Used (mg) Delivery Delivery

Esen et al,49 1999 Yes Mand 0 20 0 20 22 Methylprednisolone 125 IV Preop

sodium succinate
Holland,57 1987 Yes Mand 0 20 0 20 23.4 Methylprednisolone 40 IV Preop
Milles et al,58 1993 Yes Max/mand 0 11 1 11 24 Methylprednisolone 20 IV Preop
Skjelbred and Løkken,52 1982 Yes Max/mand 0 24 0 24 24 Betamethasone 9 IM Preop
Skjelbred and Løkken,53 1982 Yes Max/mand 0 12 0 12 23 Betamethasone 9 IM Postop
Neupert et al,63 1992 Yes Max/mand 2 60 2 60 18-24 Dexamethasone 4 IV Preop
Baxendale et al,59 1993 Yes Max/mand 0 25 0 25 22.8 Dexamethasone 8 Oral Preop
Schmelseizen and Frölich,60 1989 Yes Max/mand 5 26 3 25 18 Dexamethasone 6 Oral Preop ⫹ postop
Pedersen,69 1985 Yes Mand 0 30 0 30 22 Dexamethasone 4 IM Preop
Abbreviations: CS, corticosteroid; IM, intramuscular; IV, intravenous; mand, mandibular teeth surgically removed; max, maxillary teeth surgically removed; postop,
postoperative; preop, preoperative.

2211
NOTE. Table lists the number of infections in the CS versus control groups in various clinical oral surgery trials, in which a CS was administered. All studies were randomized,
double-blind studies tested against placebo (saline).
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.
2212 CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY

A
Dose Methylprednisolone (mg)
Reference number in square.
Black = Significant edema reduction
Red = No significant edema reduction
130
56 49

120
52 Skjelbred and Løkken, 1982A,
Betamethasone, IM, P<0,001

Beirne and Hollander, 1986,

56
Methylprednisolone, IV, P<0,05

49 Esen et al, 1999, Methylprednisolone-

70 sodium succinate, IV, P<0,005

61 Buyukkurt et al, 2006, Prednisolone,

IM, P = 0,001

60 52 53
62 Graziani et al, 2006, Dexamethasone,
Submucosal injection, P<0,001

60 Schmelseizen and Frolich, 1989,

Dexamethasone, Oral, P<0,056
50
53 Skjelbred and Løkken, 1982B,
Betamethasone, IM, P=0,006

40 57 59 Baxendale et al, 1993, Dexamethasone,

Oral, P<0,05

59
57 Holland et al, 1987,
Methylprednisolone, IV, P=0,0003
30 58
69 Pedersen et al, 1985, Dexamethasone,
60 60 IM, P<0,001

69 63 62
20 61 58 Milles et al, 1993, Methylprednisolone,
IV, P<0,001

63 Neupert et al, 1992, Dexamethasone,

IV, P = Not significant
10

Administration time
Pre-operative Peri-operative Post-operative

FIGURE 1. A, Comparison of administration time (x axis) and dose of methylprednisolone in milligrams (y axis) shows significant (P ⬍ .05, black squares)
versus nonsignificant (P ⬎ .05, red squares) decreases in edema by CS administration in oral surgery at different doses, times of treatment onset, and
durations of treatment. Studies are cited (within squares) and those connected with a line indicate that more than 1 dose was given at different administration
times. B, Forest plot of number of edema events (CS use in oral surgery) shows a comparison of 6 selected trials in which a CS (experimental) versus placebo
(control) has been administered. With each trial, the number of events (severe or moderate edema) has been noted. A schematic graph (center) shows the
selected trials according to the combined estimated RR (RR ⬎1 ⫽ increased risk of postoperative edema). On the right side, RR (95% CI), W (fixed), and
W (random) values are displayed. CI, confidence interval; CS, corticosteroid; IM, intramuscular; IV, intravenous; RR, relative risk; W, normal distribution.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.

or no/mild edema (results from the second and third showing a lower risk. The confidence intervals of all 6
postoperative days). Figure 1B shows the RR of edema studies overlap, and a formal assessment of heterogene-
for the CS compared with the placebo group, and indi- ity using the Cochran ␹2 test for homogeneity (statistics
vidual estimates of RR are quite consistently below 1, test, Q5 ⫽ 15.01, P ⫽ .0103, I2 ⫽ 66.7% [20.5%, 86%])
DAN, THYGESEN, AND PINHOLT 2213

A
Dose Methylprednisolone (mg)
Reference number in square.
Black = Significant post-op pain reduction
Red = No significant post-op pain reduction
130
56 49

120
52 Skjelbred and Løkken, 1982A,
Betamethasone, IM, P < 0,001

Beirne and Hollander, 1986,

56
Methylprednisolone, IV, P < 0,01

49 Esen et al, 1999, Methylprednisolone-

70 sodium succinate, IV, P < 0,0001

62 Graziani et al, 2006, Dexamethasone,

Submucosal injection, P = 0,02

60 52 53 60 Schmelseizen and Frolich, 1989,

Dexamethasone, Oral, P = 0,01

59 Baxendale et al, 1993, Dexamethasone,

Oral, P < 0,005
50
Neupert et al, 1992, Dexamethasone,
63
IV, P < 0,0001

Pedersen et al, 1985, Dexamethasone,

40 69
IM, P > 0,05

59
58 Milles et al, 1993, Methylprednisolone,
IV, P > 0,05
30 58
61 Buyukkurt et al, 2006, Prednisolone,
60 60 IM, P > 0,05

69 63 62
20 61 53 Skjelbred and Løkken, 1982B,
Betamethasone, IM, P > 0,1

10

Administration time
Pre-operative Peri-operative Post-operative

FIGURE 2. A, Comparison of administration time (x axis) and dose of methylprednisolone in milligrams (y axis) shows significant (P ⬍ .05,
black squares) versus nonsignificant (P ⬎ .05, red squares) decreases in pain by CS administration in oral surgery at different doses, times
of treatment onset, and durations of treatment. Studies are cited (within squares) and those connected with a line indicate that more than 1
dose was given at different administration times. B, Forest plot of number of analgesia events (CS use in oral surgery) shows a comparison
of 5 selected trials in which a CS (experimental) versus placebo (control) was administered. With each trial, the number of events
(postoperative analgesia) is noted. A schematic graph (center) shows the selected trials according to the combined estimated RR (RR ⬎1 ⫽
increased chance of postoperative analgesia). On the right side, RR (95% CI), W(fixed), and W(random) values are displayed. CI, confidence
interval; CS, corticosteroid; IM, intramuscular; IV, intravenous; RR, relative risk.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.
2214 CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY

Dose Methylprednisolone (mg)

Reference number in square.
Black = Significant Edema reduction
Red = No significant Edema reduction
170
72
160

70 Weber and Griffin, 1994,

Dexamethasone, IV, P < 0,05

71 Peillon et al, 1996,

Methylprednisolone, IV, P = Not available

110 72 Munroe et al, 1986,

Dexamethasone, IV, P > 0,05

100

90 71 71 71 71

70 70

80 72 72 72 72

70

60

50
70 70
Administration time
40
Pre-operative Peri-operative Post-operative 1st post-op day 2nd post-op day 3rd post-op day

FIGURE 3. Comparison of administration time (x axis) and dose of methylprednisolone in milligrams (y axis) shows significant (P ⬍ .05, black
squares) versus nonsignificant (P ⬎ .05, red squares) decreases in edema by corticosteroid administration in orthognathic surgery at different
doses, times of treatment onset, and durations of treatment. Studies are cited (within squares) and those connected with a line indicate that
more than 1 dose was given at different administration times.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.

shows a consistency across studies and that the com-
bined estimate of RR can be trusted.
The ␹2 test on the selected data52,53,56-59 shows that
when CS has been administered, the estimated RR of
postoperative edema is 0.4065 (0.2917, 0.5666) com-
pared with placebo, a highly significant result (P ⬍
.0001, Z ⫽ ⫺5.3153) allowing the conclusion that CS
administration does decrease the risk of postoperative
edema significantly.
Analgesia
Regarding CS administration and decreased pain in
oral surgery, 11 articles49,52,53,56,58-62,63,69 were se-
lected and divided into 2 groups: 7 trials that showed
significantly decreased pain after administration of
CS49,52,56,59,60,62,63 and 4 with no significant analgesic
effect of CS.53,58,61,69
Figure 2A shows the magnitude of available trials
that have shown the pain-decreasing effect of CS after
oral surgery. Four trials showed no significant analge-
sic effect of CS,53,58,61,69 with 358,61,69 placed in the
lower quadrant of Figure 2A, indicating a relation to
the CS dose administered, and 253,69 of the 4 trials in
the section of postoperative administration time, in-
dicating that this might be too late to facilitate an
analgesic effect of CSs.
Six studies49,52,56,59,60,62 reported decreased edema
and analgesia, 4 studies53,58,61,69 reported decreased
edema and no analgesia, and 1 study63 reported de-
creased edema but no analgesia, indicating a relation
between the dose (and degree of edema) and postop-
erative pain. No trial showed an increased need for
analgesic treatment postoperatively after CS adminis-
tration.2,49,52,53,56,58-62,63,67,69 Of these available 11 ar-
ticles, 5 articles52,53,56,59,63 provided sufficient data to
be included in the meta-analysis. A forest plot of the
selected 5 articles was made.
Figure 2B shows the results from 5 randomized
clinical trials of 269 bilateral M3 surgery sites treated
with CS or placebo with the composite endpoint
being postoperative no pain or pain (results from the
first postoperative day). Figure 2B shows the RR of
analgesia for the CS compared with placebo group,
and individual estimates of RR vary quite consider-
ably, but are all above 1, showing an increased rate of
postoperative analgesia using CSs. The confidence
intervals of all 5 studies overlap, and a formal assess-
DAN, THYGESEN, AND PINHOLT
ment of heterogeneity using the Cochran ␹2 test for
homogeneity shows a consistency across studies (sta-
tistics test, Q4 ⫽ 18.67, P ⫽ .0009, I2 ⫽ 78.6% [48.8%,
91%]) and that the combined estimate of RR can be
trusted.
The ␹2 test showed an estimated relative rate of
analgesia with CS of 2.8824 (1.9579, 4.2437) com-
pared with placebo (P ⬍ .0001, Z ⫽ 5.3644), indicat-
ing that CS administration decreases the risk of post-
operative pain significantly.
CORTICOSTEROID ADMINISTRATION IN
ORTHOGNATHIC SURGERY
Edema
Two reviews concerning orthognathic surgery sup-
ported the administration of CSs when edema or vas-
cular problems were to be expected.76,77
Five clinical trials were conducted,1,4,70-72 and 2
were abandoned because they were neither random-
ized nor double-blinded.1,4 This left 3 well-conducted
trials,70-72 with 2 showing a significant decrease in
edema70,71 and 1 that did not.72
In all trials represented in Figure 3, CSs were admin-
istered through an intravenous route, but at different
doses, times of onset, and durations of treatment.
A trial by Munro et al72 did not show any significant
decrease in edema but is among the trials in which
the highest doses and the longest durations of treat-
ment were used.1,72 The researchers stated that the
lack of effect was due to hormonal differences be-
cause all patients were children. This seems plausible
but was not possible to clarify by the literature re-
viewed in the present study. Another problem in this
study could be the grading of clinical edema on a
simple scale from 0 to 4, which is not as accurate as
the objective measurement method used in the other
studies, examples being computed tomographic
scans, C-reactive protein values,72 and laser scans.71
A trial by Weber and Griffin70 published in 1994
showed significantly decreased edema with 1 single
preoperative dose of dexamethasone and doses admin-
istered before and after surgery and on the first postop-
erative day. This trial concluded that, if minimum dose
and duration are preferred, administration of methyl-
prednisolone 85 mg (intravenously) preoperatively
seems to decrease edema significantly, but more clinical
trials are needed to support this conclusion.
No meta-analysis could be performed in orthog-
nathic surgery and decreased edema with CSs; further
clinical trials are needed.
Neuroregeneration
A trial by Al-Bishri e al,13 which was based on the
patients’ own evaluation of neurosensory dysfunc-
tion, was not included because of the purely subjec-
tive evaluation method.
2215
Bracken et al78 advocated the use of 24-hour methyl-
prednisolone (initially 30 mg/kg before the operation
and thereafter a methylprednisolone infusion of 5.4 mg/
kg/h) if started sooner than 3 hours after trauma and of
48-hour methylprednisolone (2.5-mg/kg bolus infusion
of tirilazad mesylate every 6 hours) if longer than 3
hours after trauma, and both regimens had significant
neuroregeneration effects. Seo et al12 administered a
fixed CS dose (prednisolone 30 mg for 7 days, 15
mg for 4 days, and 5 mg for 3 days) during 14 days
of treatment with different times for onset of treat-
ment (1 week, 3 weeks, or 6 weeks after trauma)
and found significant neuroregeneration in patients
when treatment onset was later than the first week
after trauma.
A study by Galloway et al79 showed that an initial
neuroregeneration effect was not statistically signifi-
cant.
Combined, these studies show that there might be
a neuroregeneration effect of CSs, but no meta-analy-
sis could be performed, and further clinical studies
are needed.
Side Effects
Adrenal suppression. Several investigators have
concluded that the administration of CSs results in
temporary adrenal suppression.28,45-49
Long-term states of adrenal suppression are claimed
to occur at random if the dose administered is hydro-
cortisone ⬎20 mg (methylprednisolone ⬎4 mg)25 or
prednisolone ⬎50 mg (methylprednisolone ⬎40
mg)26 and when the dose is higher than physiologic
levels for longer than 5 days27-29 or is administered for
longer than 1 to 2 weeks of treatment.30 This indi-
cates that an increased risk is to be expected with the
administration of doses, although low, used for oral
and orthognathic surgeries because the administra-
tion period is shorter than 5 days. No meta-analysis
could be done to verify this, and further studies are
needed.
Steroid-induced psychosis. A trial by Lewis and
Smith40 concluded that women have an increased risk
of steroid-induced psychosis because of hormonal dif-
ferences. A history of psychotic behavior has also
been associated with a higher risk,41 although some
investigators could not relate risk to prehistory.14 Sev-
eral trials have concluded that the risk of psychosis is
significantly increased when a dose of prednisolone
⬎40 mg (methylprednisolone ⬎32 mg) is adminis-
tered.42,43 Galen et al14 showed that higher doses
induce a higher risk, and Flemming and Flood44
linked an increased risk to the use of a CS with a long
half-life.
These findings indicate an increased risk using a CS
with a long half-life (betamethasone and dexametha-
2216
FIGURE 4. Forest plot of number of events without infection (corticosteroid use in oral surgery) shows a comparison of 9 selected trials in
which a corticosteroid (experimental) versus placebo (control) was administered. With each trial, the number of events (number of no
postoperative infections) has been noted. A schematic graph (center) shows the selected trials according to the combined estimated RR (RR
⬎1 ⫽ increased risk of postoperative infection). On the right side, RR (95% CI), W (fixed), and W (random) values are displayed. CI,
confidence interval; RR, relative risk.
Dan, Thygesen, and Pinholt. Corticosteroids in Oral/Orthognathic Surgery. J Oral Maxillofac Surg 2010.
sone) and with doses of methylprednisolone ⬎32 mg,
which is the case for the dose advocated for orthog-
nathic surgery. No meta-analysis could be performed
on the topic of CS inducing steroid-induced psycho-
sis, and further clinical studies are needed.
Avascular osteonecrosis. Some investigators have
found that high CS dosages, even for shorter periods,
increase the risk of avascular osteonecrosis.17-20 Oth-
ers have claimed that a dose of dexamethasone ⬎16
mg daily (methylprednisolone ⬎85 mg)21 or methyl-
prednisolone ⬎1,830 mg over the first 30 hours22,23
also increases the risk.
A large study by Precious et al78 with 2,773 patients
showed retrospectively that there were no increased
risk of femoral head necrosis and subsequent need for
hip replacement in patients who received orthog-
nathic surgery and were treated with high-dose short-
duration CS. Other factors such as smoking, alcohol
consumption, and work are also thought to predis-
pose to the development of avascular osteonecrosis.24
These findings indicate that an increased risk is
seen with doses of methylprednisolone ⬎85 mg (or-
thognathic surgery); no meta-analysis could be per-
formed, and further studies are needed.
Increased infection rate and decreased healing. In
animal studies, decreased healing is associated with
CS administration.33-35 Conversely, in human studies,
none of the trials available reported signs of decreased
healing,2,3,49,52,53,57-59,63,69 and with a reduced heal-
ing rate incidence of zero, no meta-analysis could be
performed. The result being that the administration
of CS does not induce a significantly reduced heal-
ing rate.
Regarding infection rate, several clinical human stud-
ies have concluded that no increased infection rate is
seen because of CS administration.2,3,49,52,53,57-60,63,69
Huffman3 reported that 2 subjects in the control group
CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY
and 1 in the steroid group had an infection. Milles and
Desjardins58 reported 1 infection in the placebo
group. Neupert et al63 reported 2 infections in the CS
and placebo groups. Schmelzeisen and Frölich60 re-
ported 3 infections in the placebo group and 5 in
the CS group. A forest plot of the selected 9 arti-
cles49,52,53,57-60,63,69 was created.
Figure 4 shows the results from 9 randomized clin-
ical trials of 434 bilateral M3 surgery sites treated with
CS or placebo with the composite endpoint being
postoperative infection or no infection (results from
the first postoperative week). Figure 4 shows the RR
of infection for the CS compared with placebo group,
and individual estimates of RR are quite consistent at
1 straight, with 2 exceptions at 0.91 and 1.10, indi-
cating no increased risk of postoperative infection in
either group. The confidence intervals of all 9 studies
overlap, and a formal assessment of heterogeneity
using the Cochran ␹2 test for homogeneity (statistics
test, Q8 ⫽ ⬁, P ⬍ .0001, I2 ⫽ NaN% [NaN%, NaN%])
shows a consistency across studies and that the com-
bined estimate of RR can be trusted.
The ␹2 test shows an estimated RR of 1.0041
(0.9451, 1.0669) for CS compared with placebo, indi-
cating a slightly higher but nonsignificant risk of in-
fection (P ⫽ .8937, Z ⫽ 0.1336) and that CSs do not
increase the risk of infection significantly.
In all available trials in orthognathic surgery, anti-
biotics were administered, and thus these trials can-
not be used to conclude any increased risks of
infection.1,4,70-72
Discussion
The aim of this review was to confirm or reject the
edema-decreasing effect of CS administration in sur-
gical extraction and orthognathic surgery.
DAN, THYGESEN, AND PINHOLT
In surgical extraction, most trials showed a sig-
nificant decrease in edema after CS administration
using different doses, routes, and durations of treat-
ment,49,52,53,56-62,69 with ␹2 test showing an esti-
mated RR of edema of 0.4 compared with placebo
(P ⬍ .0001), indicating that CS administration de-
creases the risk of postoperative edema signifi-
cantly.
In oral surgery, the threshold dose value of meth-
ylprednisolone is expected to be 0 to 25 mg, above
which any single dose of methylprednisolone ad-
ministered will result in a significant decrease in
edema. This indicates that if a minimum dose is
preferable, a preoperative injection into the masse-
ter muscle of methylprednisolone ⱖ25 mg (or an
equivalent anti-inflammatory dose of another CS) is
effective in decreasing edema.
In orthognathic surgery, fewer trials are available,
but these show a significant decrease of edema when
CSs are administered at different doses and durations
of treatment.70,72 It seems plausible that 1 intravenous
dose of methylprednisolone ⱖ85 mg (or an equiva-
lent anti-inflammatory dose of another CS) adminis-
tered preoperatively results in a significant decrease
in edema, but more research is needed to verify this.
Insufficient data on the edema-decreasing effect of CS
after orthognathic surgery did not allow a meta-anal-
ysis.
No trials reported an increased need of analge-
sic treatment postoperatively after CS administra-
tion.49,52,53,56,58-63,69 This shows that CS administra-
tion does not suppress the ␤-endorphin level and
thereby increase the patient’s perception of pain.8
Several trials reported significantly decreased
edema and analgesia,49,52,56,59,60,62 indicating a strong
correlation between edema and pain decreases. How-
ever, Pedersen,69 Skjelbred and Løkken,53 Buyukkurt
et al,61 and Milles et al58 found a significant decrease
in edema but no significant decrease in pain con-
nected to the low dose58,61,69 and/or postoperative
administration timing.53,69 Neupert et al63 found no
significant decrease in edema but a significant de-
crease in pain. A ␹2 test showed that the estimated
RR of analgesia with CS is 2.9 compared with placebo
(P ⬍ .0001), indicating that CS administration de-
creases the risk of postoperative pain significantly.
Human trials on CS and neuroregeneration indi-
cated that CS promotes neuroregeneration.12,13,78
However, there is no accepted conclusion on what
should be the administered dose or the onset and
duration of treatment to support the conclusions pre-
sented.
In their animal study, Galloway et al79 concluded
that a primary neuroregeneration effect was not sta-
tistically significant. Further clinical trials are needed.
2217
Although rare, long-term adrenal suppression seems
to take place unpredictably with doses of methylpred-
nisolone ⬎4 mg (above physiologic levels)25,26 for
longer than 5 days27-29 and when the treatment dura-
tion is longer than 1 to 2 weeks, regardless of the
dose.30 Female gender40 and a history of psychotic
behavior41 were found to increase the risk of steroid-
induced psychosis. This was, however, not well-doc-
umented in the literature, and other researchers dis-
agree.14 There seems to be a connection between an
increased risk and a dose of prednisolone ⬎40 mg/
day,14,42,43 especially when using a CS with a long
half-life.44 Further clinical trials are needed.
Avascular osteonecrosis seems to occur more fre-
quently with high dosages.17-20 Doses of dexametha-
sone ⬎16 mg/day21 and methylprednisolone ⱕ1,830
mg within 30 hours22,23 are expected to increase the
risk. A retrospective study of 2,773 patients treated
with high-dose, short-duration CS administration con-
cluded that none of the patients developed avascular
osteonecrosis in the subsequent 1 to 5 years.78 There-
fore, it seems that there is a minimally increased risk
when administering high-dose CS over a short period.
Other predisposing factors such as smoking, alcohol
consumption, and hard physical labor are also
thought to increase the risk.24 Further clinical trials
are needed.
Regarding increased infection rates, in oral surgery, most
trials reported infection rates49,52,53,57-60,63,69 and only 160
found an increased risk. A ␹2 test showed an esti-
mated RR of 1.0041 for CS compared with placebo,
indicating a slightly higher but nonsignificant risk of
infection (P ⫽ .89) and that the administration of CS
did not increase the risk of infection significantly.
Hence, there is no significantly increased risk of in-
fection and the use of prophylactic antibiotics should
not be administered, unless other indications are
present.
The fear of CSs causing decreased healing has shown to
be less plausible, because none of the available trials re-
ported any signs of this.2,3,49,52,53,57-59,63,69
Some factors present in this study might be per-
ceived by others as problematic. With respect to the
review, the division of the available articles on edema
and pain into only 2 categories, those with and those
without significant decreases in edema and/or pain,
makes this study less sensitive to gradual changes
because even the slightest decrease in edema will be
registered in the same way as a substantial decrease.
However, the aim of this study was to evaluate
whether any decrease in edema and pain was present,
not to determine the degree of edema and/or pain.
The lack of differentiation between the methods
used to evaluate edema and pain (in the respective
clinical trials) also makes this study less sensitive. This
was considered; however, all selected trials were sig-
2218
nificant with regard to their respective studies and
were compared in this regard.
With regard to the meta-analysis, edema is believed
to be greater in the mandible, and the comparison of
studies including only mandibular or maxillary and
mandibular M3 surgical extractions could be viewed
as a potential bias. However, because maxillary and
mandibular extractions were done bilaterally and in a
double-blind manner (including the upper and lower
jaws on the same side during the same operation),
this was considered to be of lesser importance.
Regarding the evaluation of edema, 4 stud-
ies52,53,56,57 used a mechanical device/facebow, 1
study59 used a facial plethysmograph, and 1 study58
used an observer to grade the facial edema. Using an
observer was less precise than the other 2 methods,
but acceptable, because it was the same observer
who graded all edemas.
With respect to analgesia, postoperative pain was
evaluated in 3 different ways; 3 studies52,53,59 used a
visual analog scale, 1 study56 used number of tablets
(medication diary), and 1 study63 let the patient
choose the least painful side. We chose these 3 dif-
ferent ways to quantify postoperative pain as the
same.
Whether these findings can be extrapolated to
other surgical fields, such as apicoectomy, implant
dentistry, treatment of odontogenic pathologic condi-
tions, and traumatic fractures, is difficult to conclude
from this review. It seems plausible that if an inflam-
matory reaction is present and thus edema and pain
are expected, the administration of a CS preopera-
tively would be expected to decrease edema and
pain, thereby causing fewer postoperative complica-
tions.
In conclusion, these findings suggest that CS admin-
istered in combination with oral surgery produces
significant decreases in edema and pain (P ⬍ .0001
for both comparisons).
A nonsignificant (P ⫽ .8937) increased infection
rate (RR, 1.0041) after CS administration compared
with placebo shows that antibiotic prophylaxis in
combination with a CS is not indicated unless other
indications are present.
A minimal risk of developing temporary adrenal
suppression is present because of the administration
of a CS in the dose required for oral surgery (preop-
erative injection in the masseter muscle of methyl-
prednisolone ⱖ25 mg or equivalent drug). Thus far,
there is no evidence of other side effects, but further
research is needed to verify this.
In orthognathic surgery, it seems a preoperative
intravenous dose of methylprednisolone ⱖ85 mg or
an equivalent drug results in decreased edema, but
this needs further research. Most trials showed that
CSs contribute to neuroregeneration, but further stud-
CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY
ies are needed. An elevated risk for the development
of avascular necrosis, steroid-induced psychosis, and
adrenal suppression is present with the higher dosage
required for orthognathic surgery advised in this anal-
ysis.
The present findings suggest that the administra-
tion of CSs in oral surgery decreases edema and pain
significantly, with no higher risk of infection and with
minimum risk of other side effects.
Acknowledgment
The authors thank Thomas Alexander Gerds, Associate Professor
(Department of Biostatistics, University of Copenhagen, Copenha-
gen, Denmark), for the statistical analysis performed.
References
1. Guernsey LH, DeChamplain RW: Sequelae and complications
of the intraoral sagittal osteotomy in the mandibular rami.
J Oral Surg 32:176, 1971
2. Hooley JR, Francis FH: Betamethasone in traumatic oral sur-
gery. J Oral Surg 27:395, 1969
3. Huffman G: Use of methylprednisolone sodium succinate to
reduce post-operative edema after removal of impacted third
molars. J Oral Surg 35:198, 1977
4. Schaberg SJ, Stuller CB, Edwards SM: Effect of methylpred-
nisolone on swelling after orthognathic surgery. J Oral Maxil-
lofac Surg 42:356, 1984
5. Grollman A, Grollman EF: Pharmacology and Therapeutics (ed
7). Philadelphia, Lea and Febiger, 1970, p 758
6. Hong SL, Levine L: Inhibition of arachidonic acid release from
cells as the biochemical action of anti-inflammatory corticoste-
roids. Proc Natl Acad Aci U S A 73:1730, 1976
7. Blackwell GJ, Carnuccio R, Rosa M: Glucocorticoids induce the
formation and release of anti-inflammatory and anti-phospho-
lipase proteins into the peritoneal cavity of the rat. Br J Phar-
macol 76:185, 1982
8. Hargreaves KM, Costello A: Glucocorticoids suppress levels of
immunoreactive bradykinin in inflamed tissue as evaluated by
microdialysis probes. Clin Pharmacol Ther 48:168, 1990
9. Melby J: Systemic corticosteroid therapy: Pharmacology and
endocrinologic considerations. Ann Intern Med 81:505, 1974
10. Tam S, Hong SL, Levine L: Relationships among the steroids of
anti-inflammatory properties and inhibition of prostaglandin
production and arachidonic acid release by transformed mouse
fibroblasts. J Pharmacol Exp Ther 203:162, 1977
11. Berne RM, Levy MN, Koeppen BM, Stanton BA: Physiology (ed
5). St Louis, MO, Mosby/Elsevier, 2004, p 894
12. Seo K, Tanaka Y, Terumitsu M, Someya G: Efficacy of steroid
treatment for sensory impairment after orthognathic surgery.
J Oral Maxillofac Surg 62:1193, 2004
13. Al-Bishri A, Rosenquist J, Sunzel B: On neurosensory distur-
bance after sagittal split osteotomy. J Oral Maxillofac Surg
62:1472, 2004
14. Galen DM, Beck M, Buchbinder D: Steroid psychosis after
orthognathic surgery: A case report. J Oral Maxillofac Surg
55:294, 1997
15. Melby J: Adrenocorticoids in medical emergencies. Med Clin
North Am 45:875, 1961
16. Themistocles LA, Lessard LM: The use of perioperative corti-
costeroids in craniomaxillofacial surgery. Am Soc Plast Surg
103:313, 1999
17. Gold DA, Adelwahab ID, Hermann G: Osteonecrosis of both
medial tibial condyles following short-term steroid therapy. A
case report. Bull Hosp Jt Dis Orthop Inst 49:103, 1989
18. Fast A, Alon M, Weiss S, Zer-Aviv FR: Avascular necrosis of bone
following short-term dexamethasone therapy for brain edema.
Case report. J Neurol Surg 61:983, 1984
DAN, THYGESEN, AND PINHOLT
19. Grossmann S, Ganz R: Osteonecrosis following short-term,
high-dosage steroid therapy. Schweiz Med Wochenschr 121:
635, 1991
20. Foley-Nolan D, Daly C, Barry C, et al: Avascular necrosis of the
femoral head post heart-transplantation and steroid dosage. Ir
Med J 85:138, 1992
21. Anderten JM, Helm R: Multiple joint osteonecrosis following
short term steroid therapy: Case report. J Bone Joint Surg Am
64:139, 1982
22. Black KA, Khangure MS, Owen ET: Dexamethasone and osteo-
necrosis. Aust N Z J Med 11:521, 1981
23. Mccluskey J, Gutheridge DH: Avascular necrosis of bone after
high doses of dexamethasone during neurosurgery. BMJ 284:
333, 1982
24. Hirota Y, Hirohata T, Fukuda K, et al: Association of alcohol
intake, cigarette smoking, and occupational status with the risk
of idiopathic osteonecrosis of the femoral head. Am J Epide-
miol 137:530, 1993
25. Cawson RA, James J: Adrenal crisis in a dental patient having
systemic corticosteroid. Br J Oral Surg 10:305, 1973
26. Spiegel RJ, Vigersky RA, Oliff AI, et al: Adrenal suppression
after short-term corticosteroid therapy. Lancet 1:630, 1979
27. Axelrod L: Glucocorticoid therapy. Medicine (Baltimore) 55:
39, 1976
28. Streck WF, Lockwood DH: Pituitary adrenal recovery following
short-term suppression with corticosteroids. Am J Med 66:920,
1979
29. Little JW, Falace DA: Adrenal Insufficiency in Dental Manage-
ment of the Medically Compromised Patient (ed 3). St Louis,
MO, Mosby, 1988, p 309
30. Pedersen C, Bjerrum L, Dalhoff KP, et al (eds): Medicin.dk,
Informatum A/S, Denmark, pp 249-251, 2009
31. Chedid M, Hoyle JR, Csaky KG, et al: Glucocorticoids inhibit
keratinocyte growth factor production in primary dermal fibro-
blasts. Endocrinology 137:2232, 1996
32. Bahn S: Glucocorticosteroids in dentistry. J Am Dent Assoc
105:475, 1982
33. Durmus M, Karaaslan E, Ozturk E, et al: The effects of single-
dose dexamethasone on wound healing in rats. Anesth Analg
97:1377, 2003
34. Tydd JJ, Tydd M: The effects of cortisone acetate on tissue
regeneration in the rabbits ear. J Anat 115:445, 1973
35. Marks JG, Cano C, Leitzel K: Inhibition of wound healing by
topical steroids. J Dermatol Surg Oncol 9:819, 1983
36. Brown ES, Vazquez M, Nakamura A: Randomized, placebo-
controlled, crossover trial of memantine for cognitive changes
with corticosteroid therapy. Biol Psychiatry 64:727, 2008
37. Gersema L, Baker K: Use of corticosteroids in oral surgery.
J Oral Maxillofac Surg 50:270, 1992
38. Alexander RE, Throndson RR: A review of perioperative corti-
costeroid use in dentoalveolar surgery. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 90:406, 2000
39. Montgomery MT, Hogg JP, Roberts DL, Redding SW: The use of
glucocorticoids to lessen the inflammatory sequelae following
third molar surgery. J Oral Maxillofac Surg 48:179, 1990
40. Lewis DA, Smith RE: Steroid-induced psychiatric syndromes. J
Affect Disord 5:319, 1983
41. Garner HH, Falk MA: Toxic psychosis: Pemphigus and psychi-
atric diseases. Psychosomatics 8:133, 1967
42. Hall RC, Popkin MK, Stickney SK: Presentation of the steroid
psychosis. J Nerv Ment Syst 167:229, 1979
43. Silva RG, Tolstunov L: Steroid-induced psychosis: Report of
case. J Oral Maxillofac Surg 53:183, 1995
44. Flemming PS, Flood TR: Steroid-induced psychosis complicat-
ing orthognathic surgery: A case report. Br Dent J 199:647,
2005
45. Jacobs JWG, Biljsma JWJ: Glucocorticoids, in Ruddy S et al,
(eds): Kelly’s Textbook of Rheumatology. New York, Elsevier,
2005, pp 859-876
46. Williamson LW, Lorson EL, Osbon DB: Hypothalamic-pituitary-
adrenal suppression after short-term dexamethasone therapy
for oral surgical procedures. J Oral Surg 38:20, 1980
2219
47. Hooley JR, Bradle PB, Haines M: Plasma cortisol levels follow-
ing short term betamethasone therapy for oral surgical proce-
dures. Trans Int Conf Oral Surg 4:188, 1973
48. Butler RC, Voron AA, Finstuen K: Dosage effects of pulsed
steroid therapy on serum cortisol levels in oral and maxillofa-
cial surgery patients. J Oral Maxillofac Surg 51:750, 1993
49. Esen EE, Tasar F, Akhan O: Determination of the anti-inflam-
matory effects of methylprednisolone on the sequelae of third
molar surgery. J Oral Maxillofac Surg 57:1201, 1999
50. Cruess RL: Steroid-induced osteonecrosis: A review. Can J Surg
24:567, 1981
51. Hooley JR, Hohl TH: Use of steroids in the prevention of some
complications after traumatic oral surgery. J Oral Surg 32:864,
1974
52. Skjelbred P, Løkken P: Post-operative pain and inflammatory
reaction reduced by injection of a corticosteroid. A controlled
trial in bilateral oral surgery. Eur J Clin Pharmacol 21:391, 1982
53. Skjelbred P, Løkken P: Reduction of pain and swelling by a
corticosteroid injected 3 hours after surgery. Eur J Clin Phar-
macol 23:141, 1982
54. Peterson LJ: Prevention and management of surgical complica-
tions, in Peterson LJ, Ellis E, Hupp JR, Tucker MR (eds): Con-
temporary Oral and Maxillofacial Surgery. St Louis, MO: Mosby/
Elsevier, 2003, p 221
55. Mitchell DA, Ward-Booth P, Seymour RA: A comparative study
of the efficacy of aspirin and an ibuprofen/codeine combina-
tion in patients treated pre-operatively with methylpred-
nisolone acetate. Br Dent J 159:78, 1985
56. Beirne OR, Hollander B: The effect of methylprednisolone on
pain, trismus and swelling after removal of third molar. Oral
Surg Oral Med Oral Pathol 61:134, 1986
57. Holland CS: The influence of methylprednisolone on post-
operative swelling following oral surgery. Br J Oral Maxillofac
Surg 25:293, 1987
58. Milles M, Desjardins PJ: Reduction of postoperative facial swell-
ing by low-dose methylprednisolone: An experimental study.
J Oral Maxillofac Surg 51:987, 1993
59. Baxendale BR, Vater M, Lavery KM: Dexamethasone reduces
pain and swelling following extraction of third molar teeth. J
Anesth 48:961, 1993
60. Schmelzeisen R, Frölich JC: Prevention of postoperative swell-
ing and pain by dexamethasone after operative removal of
impacted third molar teeth. Eur J Clin Pharmacol 44:275, 1993
61. Buyukkurt MC, Gungormus M, Kaya O: The effect of a single
dose prednisolone with and without diclofenac on pain, tris-
mus and swelling after removal of mandibular third molars.
J Oral Maxillofac Surg 64:1761, 2006
62. Graziani F, Aiuto F, Arduino P, et al: Perioperative dexameth-
asone reduces post-surgical sequelae of wisdom tooth removal.
A split-mouth randomized double-masked clinical trial. J Oral
Maxillofac Surg 35:241, 2006
63. Neupert EA III, Lee JW, Philput CB, Gordon JR: Evaluation of
dexamethasone for reduction of postsurgical sequelae of third
molar removal. J Oral Maxillofac Surg 50:1177, 1992
64. ElHag M, Coghlan K, Christmas P: The anti-inflammatory effects
of dexamethasone and therapeutic ultrasound in oral surgery.
Br J Oral Maxillofac Surg 23:17, 1985
65. Ordulu M, Aktas I, Yalcin S: Comparative study of the effect of
tube drainage versus methylprednisolone afer third molar sur-
gery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:96,
2006
66. Mead SV, Lynch DF, Mead SG: Triamcinolone given orally to
control postoperative reactions to oral surgery. J Oral Surg
22:484, 1964
67. Messer EJ, Keller JJ: The use of intraoral dexamethasone after
extraction of mandibular third molars. Oral Surg Oral Med Oral
Pathol 40:594, 1975
68. Linenberg W: The clinical evaluation of dexamethasone in oral
surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
20:6, 1965
69. Pedersen A: Decadron phosphate in the relief of complaints
after third molar surgery. A double-blind, controlled trial with
bilateral oral surgery. Int J Oral Surg 14:235, 1985
2220
70. Weber CR, Griffin JM: Evaluation of dexamethasone for
reducing postoperative edema and inflammatory response
after orthognathic surgery. J Oral Maxillofac Surg 52:35,
1994
71. Peillon D, Bubost J, Roche C, et al: La cortocothérapie et
l’hémodilution diminuent-elles I’inflammation postopératoire
apés chirurgie maxillofaciale? Ann Fr Anesth Réanim 15:157, 1996
72. Munro IR, Boyd JB, Wainwright DJ: Effect of steroids in max-
illofacial surgery. Ann Plast Surg 17:440, 1986
73. Hedges LV, Olkin I: Statistical Methods for Meta-Analysis. Or-
lando, Academic Press, 1985
74. Fleiss JL: The statistical basis of meta-analysis. Stat Methods
Med Res 2:121, 1993
CORTICOSTEROIDS IN ORAL/ORTHOGNATHIC SURGERY
75. Markiewicz MR, Brady MF, Ding EL, Dodson TB: Corticoste-
roids reduce postoperative morbidity after third molar surgery:
A systematic review and meta-analysis. J Oral Maxillofac Surg
66:1881, 2008
76. Gee J: Therapeutic use of corticosteroids in dentistry. N Y State
Dent J 40:89, 1974
77. Boc T, Peterson L: Revascularization after posterior mandibular
alveolar osteotomy. J Oral Surg 39:181, 1981
78. Precious D, Armstrong J, Morrison A, Field C: The incidence of
total hip replacement in orthognathic surgery patients receiving
short-term steroid therapy. J Oral Maxillofac Surg 50:956, 1992
79. American Medical Association Council on Drugs: New Drugs.
Chicago, American Medical Association, 1966, p 445