The use of corticosteroids and nonsteroidal antiinflammatory

medication for the management of pain and inflammation

after third molar surgery: A review of the literature
King Kim, DMD,a Pardeep Brar, DMD,b Jesse Jakubowski,c Steven Kaltman, DMD, MD,d and
Eustorgio Lopez, DDS, MD,e Fort Lauderdale, Florida
DEPARTMENT OF ORAL AND MAXILLOFACIAL SURGERY, NOVA SOUTHEASTERN
UNIVERSITY/BROWARD GENERAL MEDICAL CENTER

The use of medication to relieve pain and inflammation after removal of third molars has been explored
thoroughly in the literature. Narcotic analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, and
combinations of these all have a role in the postoperative management of pain and swelling within this group of
patients. This article addresses the use of NSAIDs and corticosteroids after third molar surgery, along with a review of
the literature, which is incorporated to provide practitioners helpful, quick, and reliable information regarding patients
undergoing third molar surgery. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:630-640)

The use of steroids in oral surgical procedures may
present as an area of ambiguity for many practitioners.
Some practitioners may consider the use of steroids
only as a supplement in patients undergoing extensive
oral surgery procedures, but steroids such as dexameth-
asone can be a valuable tool when performing moderate
to moderately severe oral surgical procedures. The use
of corticosteroids can decrease the severity of postop-
erative sequelae in many patients and therefore de-
crease morbidity after oral surgery. Many studies have
determined the effectiveness of steroids after oral sur-
gical procedures, but currently there is no standard
dosing regimen for oral and maxillofacial surgeons to
follow.1 Most practitioners follow an empiric dosing
strategy that is often inadequate and provides a sub-
therapeutic effect.
The objective of this review article is to provide
information to oral and maxillofacial surgeons on the
causes of the common postoperative sequelae after
third molar surgery, the mechanism of action of corti-
costeroids, the use of nonsteroidal antiinflammatory
drugs (NSAIDs), a review of the literature evaluating
the use of corticosteroids, the adverse effects and con-
traindications of use with corticosteroids, and recom-
a
Chief Resident.
b
Private practice, Seattle, Washington.
c
Dental student.
d
Chairman.
e
Director.
Received for publication May 21, 2008; returned for revision Sep 30,
2008; accepted for publication Nov 10, 2008.
1079-2104/$ - see front matter
© 2009 Published by Mosby, Inc.
doi:10.1016/j.tripleo.2008.11.005
mendations for the appropriate use of corticosteroids
after dentoalveolar surgery.
COMMON POSTOPERATIVE SEQUELAE AND
CAUSES OF POSTOPERATIVE SEQUELAE
AFTER ORAL SURGERY
Oral surgical procedures can vary in difficulty and in
the degree of trauma caused to the surrounding tissue.
As the oral and maxillofacial surgeon performs a more
invasive or difficult procedure, there will be an in-
creased amount of trauma to the surgical site as well as
to the surrounding tissues. The greater amount of tissue
injury leads to an increased amount of inflammation in
the perisurgical area. Swelling may be particularly sig-
nificant when the surgery is prolonged and when large
amounts of bone, gingiva, and oral mucosa are manip-
ulated. Careful surgical technique is effective in limit-
ing tissue damage and swelling; therefore, attention
should be taken to avoid prolonged periods of tissue
elevation and retraction.
The classic signs of inflammation, which include
pain, edema, erythema, and loss of function, commonly
occur after routine or difficult surgical procedures. The
inflammatory process is necessary if healing is to occur,
but often excessive inflammation causes the patient
unnecessary pain, edema, and trismus. There are many
mediators of inflammation, which include prostaglan-
dins (PGs), histamine, bradykinin, and serotonin. Pros-
taglandin and histamine levels are known to become
elevated during inflammation.2 Bradykinin has a wide
spectrum of proinflammatory pharmacology, including
potent pain-producing properties.3
Prostaglandins are derived from the precursor ara-
chidonic acid. Arachidonic acid is a major component

630
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Volume 107, Number 5
Fig. 1. Arachidonic acid cascade.4
of mammalian cell membrane phospholipids and is
released from these phospholipids via cellular phospho-
lipases that have been activated by mechanical, chem-
ical, or physical stimuli. Arachidonic acid metabolism
can proceed along 1 of 2 major pathways: the cyclo-
oxygenase pathway or the lipooxygenase pathway. The
cyclooxygenase pathway is responsible for providing
PGE2,PGD2, PGF2␣, PGI2, and thromboxane (TX) A2.
The lipooxygenase pathway leads to the formation of a
family of compounds collectively called leukotrienes.
The end products of these 2 pathways have a central
role in the inflammatory processes occurring in injured
tissue. Agents such as aspirin or NSAIDs can suppress
the cyclooxygenase pathway, whereas glucocorticoids
may act by inhibiting the activity of phospholipase A2,
thereby preventing the formation of the end products of
both pathways.
NSAID USE FOR THE MANAGEMENT OF
PAIN AND INFLAMMATION AFTER ORAL
SURGERY
NSAIDs decrease inflammation and fever while pro-
viding analgesia by inhibiting the cyclooxygenase
(COX) enzymes COX-1 and COX-2, important en-
zymes which are needed for the production of inflam-
matory mediators such as prostaglandins, prostacyclins,
and thromboxanes. Refer to Fig. 1 to review the actions
of the COX-1 and COX-2 enzymes.
Preoperative administration of NSAIDs has been in-
vestigated to determine efficacy in third molar oral
surgery patients. Some of the results of the studies
include delays in the onset of pain after surgery, de-
creased peak pain intensity, and decreased postopera-
tive swelling.5 These findings have special significance
concerning the sequelae from surgical trauma, because
the preoperative NSAID dose could decrease the
Kim et al. 631
amount of postoperative analgesics needed, especially
medications containing opiates, which tend to produce
undesirable side effects.5 In addition, studies have
shown that an appropriate NSAID regimen may be all
that is required to manage postoperative pain. NSAIDs
have been shown to provide an acceptable therapeutic
option for pain relief with fewer adverse effects than
the opioid-analgesic combination drugs.6 Also, the
many investigations done with management of acute
oral surgical pain in oral surgery patients indicate that
a single dose of an NSAID is more effective than
combinations of aspirin or acetaminophen with an opi-
oid, with fewer side effects.6
The side effects associated with the use of NSAIDs
are numerous, but primarily they are related to gastro-
intestinal (GI), hematologic, and renal disorders, as
well as the propensity to cause skin and mucosal reac-
tions.7 It should be noted that most of the manifesta-
tions of these adverse effects occur with chronic dosing
of NSAIDs. Therefore, over a long period of time, the
continuous inhibition of the COX enzymes becomes
increasingly significant.
The most profound adverse effect of the prolonged
use of traditional NSAIDs is GI disturbance. Because
this class of drugs blocks both COX enzymes, the
gastric protective functions produced from prostaglan-
dins produced by the COX-1 enzyme are not present.
This makes the GI tract susceptible to GI ulcers, dys-
pepsia, and gastric bleeding.4 It has been found that
gastric and duodenal ulcers are prevalent (15%-30% of
patients) at endoscopy in patients taking NSAIDs on a
regular basis.8 Risk factors that have been associated
with NSAIDs involve upper GI disturbances. These
include previous ulcer or upper GI event, increasing
age, concomitant anticoagulation, concomitant steroid
use, and the use of high dose or multiple NSAID use.8

632 Kim et al.
Another adverse effect of NSAID use is increased
bleeding risk intraoperatively and postoperatively. The
inhibition of COX-1 in platelets by conventional
NSAIDs results in modulation of platelet function lead-
ing to prolonged bleeding.9 This effect is longer lasting
in aspirin compared with other NSAIDs, because aspi-
rin irreversibly acetylates COX in the nonnucleated
platelet.10 Studies suggest that most conventional
NSAIDs are associated with reduced platelet aggrega-
tion in response to arachidonate and collagen and that
there is a subsequent increase in bleeding time.9 A
theoretic concern is the fact that this prolongation of
bleeding time can promote intraoperative and postop-
erative hemorrhage in dental surgical patients.10
The renal side effects of NSAIDs are also well
known and equally concerning. Normal renal function
is partly dependent on prostaglandin synthesis, and it is
believed that both COX-1 and COX-2 are important in
producing prostaglandins involved in reducing water
and sodium reabsorption which maintains proper dila-
tion of the renal vasculature. With NSAID therapy,
dose-dependent water and sodium retention manifested
by peripheral edema, elevation in blood pressure, and
rarely congestive heart failure are thought to follow the
inhibition of PGE2 synthesis.10 These NSAIDs are most
frequently associated with a transient imbalance of
electolyte and water levels that is generally mild in
most patients.9 It is estimated that serious renal prob-
lems requiring hospitalization occur in 0.5%-1.0% of
long-term NSAID users.10
The use of NSAIDs in third molar surgery is well
documented in the literature. There are numerous stud-
ies which compare NSAIDs to other NSAIDs, NSAIDs
to glucocorticoids, and NSAIDs to opioid analgesics. In
addition, comparisons are made regarding routes of
administration, timing of administration, and dosage.
Common drugs which have been investigated include:
ibuprofen, diclofenac, tramadol, ketorolac, and lomoxi-
cam. Table I summarizes relevant studies in using
NSAIDs for patients undergoing third molar surgery.
Table II compares the most commonly used NSAIDs.
MECHANISM OF ACTION OF
GLUCOCORTICOIDS
The glucocorticoids are synthesized in the cortex of
the adrenal gland. Glucocorticoids are corticosteroids
with a relatively greater effect on carbohydrate metab-
olism than on water and electrolyte regulation. Despite
the name “glucocorticoid,” they have a very broad
range of effects on many metabolic activities. Glu-
cocorticoid receptors are found in virtually every cell of
the body and exert a wide range of physiologic actions
affecting virtually every organ system.
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May 2009
Glucocorticoids activate specific intracellular recep-
tors after diffusing through target cell membranes. A
receptor-steroid complex is translocated to the cell nu-
cleus and acts as a transcription factor for specific genes
to either stimulate or inhibit their expression. It is at this
cellular level in which regulatory effects on the immune
system, including effects on cytokines, are accom-
plished. As a consequence of the time required for
changes in gene expression and de novo protein syn-
thesis, most effects of corticosteroids are not immedi-
ate, but become apparent after several hours. This fact
is of clinical significance, because a delay generally is
seen before the beneficial effects of corticosteroid ther-
apy become manifest.23
Suppression of each stage of the inflammatory re-
sponse appears to be the major action of the glucocor-
ticoids. There is a decrease in capillary dilatation, leu-
kocyte migration, and phagocytosis, a decrease in the
total number of circulating lymphocytes, basophils, eo-
sinophils, and monocytes, and an inhibition of the for-
mation of granulation tissue by retarding fibroblast
proliferation and collagen synthesis. Their major role in
reducing the inflammatory response is to inhibit the
production of vasoactive substances such as prostaglan-
dins and leukotrienes, as well as decreasing the number
of chemical attractants such as cytokines. There is also
a generalized reduction in the secretion of lipolytic and
proteolytic enzymes such as phospholipase, collage-
nase, and elastase.
Glucocorticoids also stimulate the production of li-
pocortin, which is an inhibitory protein of phospho-
lipase A2. The inhibition of phospholipase A2 leads to
a reduction in prostaglandins and leukotrienes. In ad-
dition glucocorticoids inhibit the synthesis of COX
with a resultant inhibition of PGE2 and PGI2. The use
of steroids is not curative, but palliative, and the aim is
to decrease the severity of the symptoms a patient is
anticipated to experience.23
ADVERSE EFFECTS AND CONTRAINDICATIONS
TO GLUCOCORTICOID USE IN ORAL SURGERY
The potential for adverse effects with the use of
glucocorticoids depends on the intensity and duration
of therapy. A single large dose or a short duration of
therapy causes few adverse effects. If therapy with a
glucocorticoid is prescribed for ⬎1 week, some signs
of steroid toxicity may be seen as well as signs of
hypothalamic-pituitary-adrenal (HPA) axis suppres-
sion. Adverse effects that are seen with glucocorticoids
correlate with the dose and duration of therapy. Some
adverse effects that can be seen include hyperglycemia
and glycosuria, myopathy, osteoporosis and osteone-
crosis, suppression of growth, negative nitrogen bal-
ance, peptic ulcer, ocular effects, CNS effects, edema
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Volume 107, Number 5 Kim et al. 633

Table I. Summary of several studies investigating the use of NSAIDs in oral surgery
No. of Type of
Ref. patients surgery Treatment groups Results Side effects
11 119 Removal of 1. Ibuprofen 600 mg. There was no significant difference There were, however, some side-
bilateral 2. Diclofenac 100 mg. in the extent of postoperative effects, including nausea,
impacted 3. Paracetamol 1 g with pain among the 4 groups, but the vomiting, headaches, and
third codeine 60 mg. placebo group had significantly gastrointestinal discomfort, but
molars 4. Placebo. shorter times before their first there were no significant
All given PO 1 h before request for postoperative differences among the active
surgery. analgesics (median 17 min, range analgesic groups regarding adverse
14-90 min) than the diclofenac events either shortly after
group (median 32 min, range operation or at 6 or 24 h.
15-150 min).
12 21 Removal of 1. Preop (1 h before) Patients served as their own control No information regarding side effects
bilateral diclofenac sodium 100 group. Pain scores and mouth presented.
impacted mg. opening were observed for 1
third 2. Postop (immediately week after the operation and did
molars after) diclofenac sodium not show any differences.
100 mg.
All given PO.
13 40 Removal of 1. Diflunisal 1000 mg. Patients served as their own control Side effects, including nausea,
bilateral 2. Lornoxicam 16 mg. group. No statistically significant vomiting, allergy, and
impacted All given PO 1 h before differences were found between gastrointestinal adverse effects,
third surgery. groups regarding rescue were recorded.
molars analgesic consumption and
postoperative pain scores.
Preemptive administration of
both NSAIDs proved to be
effective in the management of
pain after the surgical removal of
impacted third molar teeth.
14 55 Removal of 1. 50 mg rofecoxib. There were no significant analgesic No information was collected
bilateral 2. 400 mg ibuprofen. differences between rofecoxib regarding any possible side effects
impacted 3. Placebo. and ibuprofen at any time of the medication.
third All given PO 1 h before intervals after surgery. Rescue
molars surgery. medication use was significantly
lower in the rofecoxib and
ibuprofen groups compared with
the placebo group; however,
there was no significant
difference between the 2
therapeutic groups.
15 34 Removal of 1. IV ketorolac 30 mg, 30 Patients served as their own control No information regarding side effects
bilateral min before surgery with group . Patients reported presented.
impacted placebo injection after significantly lower pain intensity
third surgery. scores in the ketorolac pretreated
molars 2. Placebo injection, 30 min sides compared with the post-
before surgery and post- treated sides (P ⬍ .003). Patients
treated with IV ketorolac also reported a significantly
30 mg. longer time to rescue analgesic
(8.9 h vs. 6.9 h; P ⬍ .005), less
postoperative analgesic
consumption (P ⬍ .007), and
better global assessment for the
ketorolac-pretreated sides (P ⬍
.01). Pretreatment with IV
ketorolac has a preemptive effect
for postoperative third molar
surgery and extended the
analgesia by approximately 2 h.
 OOOOE
634 Kim et al. May 2009

Table I. Continued
No. of Type of
Ref. patients surgery Treatment groups Results Side effects
16 60 Removal of 1. Tramadol preop 100 mg The analgesic efficacy measured as Adverse events, such as drowsiness,
bilateral IM 1 h before surgery. complete relief of pain at 24 h dizziness, or nausea, were reported
impacted 2. Tramadol postop 100 mg was 86% in the preemptive equally across groups.
third IM immediately after tramadol compared with 70%
molars surgery. and 36% for postoperative
3. Saline before surgery. tramadol administration and
control group. A significant
reduction in the consumption of
analgesics was seen in
preoperative group compared
with the postoperative and
control groups.
17 155 Removal of 1. Preop ibuprofen (400 Patients receiving the combination ⬎Side-effects reported were mild,
bilateral mg). or ibuprofen before surgery took with no significant differences
impacted 2. Preop codeine phosphate significantly longer between between the different treatment
third (30 mg). surgery completion and needing groups.
molars 3. Preop ibuprofen/codeine the postoperative study treatment
(400 mg/30 mg), than patients receiving codeine
4. Preop placebo. phosphate or placebo. At 1.5-2 h
5. Postop single doses of the after postoperative
same combination or administration, patients receiving
diflunisal (250 mg). the combination after surgery
reported significantly greater
decreases in pain severity than
those receiving diflunisal.
Patients taking the combination
after surgery experienced
significantly better pain relief
than patients taking diflunisal at
1 and 2 h, but the reverse was
true at 5 h.
18 45 Removal of 1. Immediate postop Groups 1 and 2 suppressed pain at No information regarding side effects
bilateral prednisolone 25 mg IM. the 7th postoperative hour presented.
impacted 2. Immediate postop compared with control. Groups 1
lowerthird prednisolone 25 mg IM ⫹ and 2 also had less postoperative
molars diclofenac 100 mg IM. swelling compared with control
3. Immediate postop placebo at postoperative day 2. Group 2
IM. had a smaller loss of mouth
opening at days 2 and 7
compared with groups 1 and 3.
Group 2 had less swelling at
postoperative day 7 than groups
1 and 3.
19 72 Removal of 1. 50 mg rapid-release Double-blind, randomized, placebo- Number of side effects recorded was
single tablet, 100 mg sustained- controlled study. IV administration low in both groups.
impacted release tablet of of methylprednisolone in addition
lowerthird diclofenac, and 40 mg IV to PO diclofenac before surgery
molar methylprednisolone. gave statistically significant (P ⬍
2. 50 mg rapid-release .05) greater pain relief than
tablet, 100 mg sustained- diclofenac alone for the first 4 h.
release tablet of There was no significant
diclofenac, and 40 mg IV difference after the first 4 h or
saline. during the 2 days after surgery.
All given 20 min before The need for additional analgesics
surgery. during the day of operation and
the 2 days after was less in the
methylprednisolone ⫹ diclofenac
group than in the diclofenac
group. Maximal mouth opening
was equally decrease in both
groups from a mean of 50 mm to
36 mm
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Volume 107, Number 5 Kim et al. 635

Table I. Continued
No. of Type of
Ref. patients surgery Treatment groups Results Side effects
20 40 Removal of 1. 32 mg Patients served as their own control Side-effects reported were mild, with
4 methylprednisolone 12 h group. After use of ibuprofen/ more seen in placebo group.
symmetrical before and 12 h after methylprednisolone, ultrasonic
impacted surgery and 400 mg examination showed a reduction
third ibuprofen the day of in swelling of 56% (P ⬍ .001)
molars surgery and the 2 days compared with the placebo
following, 3⫻/day. group; measurement with a tape
2. Placebo of identical measure showed a 58% (P ⬍
appearance. .001) reduction in swelling. The
visual analog scale showed a
reduction of 67.7% in
postoperative pain compared
with placebo.
21 30 Removal of 1. 50 mg either diclofenac Preoperative administration of 50 No side effects were recorded
4 third or placebo before surgery. mg diclofenac could relieve pain
molars 2. 50 mg diclofenac and 10 and swelling more than the
mg prednisolone or placebo. Additional 10 mg
placebo before surgery prednisolone could further reduce
swelling. The combination of
diclofenac and prednisolone has
a better analgesic and
antiinflammatory effect.

Table II. Comparison of the most commonly used NSAIDs9,22

Reccomended adult Maximum daily Duration of Onset of Plasma
Drug dosage (mg) dosage (mg) action (h) action (h) half-life (h)
Ibuprofen 200-400 q 4-6 h 1,200 4-6 .5-1 2-4
Diclofenac 50 q 8 h 150 4-6 1.5-2 1-1.5
Diflunisol Initial 500-1000 then 250-500 q 8-12 h 1,500 8-12 ⬃1 8-12
Rofecoxib Initial 50 then 25 qd 75 24 2-3 17
Ketorolac 10 q 4-6 h 40 6-8 ⬃10 min 2-6
Aspirin 325-650 q 4-6 h 4,000 4-6 20-30 min 3-6
Acetaminophen 325-650 q 4-6 h 4,000 4-6 ⬍1 1-3
Naproxen Initial 500 then 250 q 6-8 h 1,250 ⬍7 1 12-17

and hyperkalemia, altered distribution of body fat, in-
creased susceptibility to infection, suppression of pitu-
itary and adrenal function, and poor wound healing.24
These effects are most commonly seen with long-term
glucocorticosteroid therapy and are very rarely seen
when administering steroids for ⬍5 days.
There is, however, a very unusual side effect which
has been documented to affect patients immediately
after administration of intravenous dexamethasone.
This side effect is perineal pruritis. This side effect has
a female predilection, lasts 30-45 s, and has been shown
to occur with dosages between 6-8 mg.25-27 The mech-
anism of this phenomenon is poorly understood. One
hypothesis is that the perineal itching and burning is
related to the phosphate ester of dexamethasone, be-
cause the same perineal irritation has been described
with hydrocortisone-21-phosphate and prednisolone
phosphate. Treatment of this side effect is administra-
tion of dexamethasone diluted in 50 mL fluid over 5-10
minutes.28
The HPA axis suppression was investigated by Wil-
liamson et al.29 by administering 8 mg dexamethasone
to patients undergoing the removal of impacted third
molar teeth. A significant difference was found be-
tween preoperative values of 11-deoxycortisol and val-
ues 3 days after surgery. No difference was found when
comparing preoperative values of 11-deoxycortisol
with values 7 days after surgery. An initial suppression
of the normal feedback mechanism of the HPA axis
was observed, and this was followed by a complete
return of normal functioning by the seventh postoper-
ative day.
Systemic and topical glucocorticoids are absolutely
contraindicated in patients with ocular herpes simplex,

636 Kim et al.
primary glaucoma, healed or incompletely healed tu-
berculosis, or acute psychosis. Relative contraindica-
tions include Cushing syndrome, diverticulitis, recent
intestinal anastomosis, active or latent peptic ulcer,
renal insufficiency, hypertension, diabetes mellitus, os-
teoporosis, myasthenia gravis, psychotic tendencies,
and acute or long-standing infections.29 It is clear from
the list of adverse effects and contraindications that the
risk/benefit ratio of steroid use must be considered
before initiation of therapy.2
REVIEW OF LITERATURE
Several studies have been conducted to evaluate the
efficacy of corticosteroids in reducing the postsurgical
sequelae experienced after oral surgical procedures,
particularly after the removal of impacted third molar
teeth. The literature contains studies that have used
methylprednisolone, betamethasone, and dexametha-
sone at various dosages and routes of administration. A
summary of the results of these studies can be viewed
in Table III.
Huffman30 in 1977 administered 40 mg and 125 mg
doses of methylprednisolone intravenously before the
removal of bilaterally impacted maxillary and mandib-
ular third molar teeth. Subjective criteria were used to
evaluate the patients 24 h, 48 h, and 7 days after
surgery. There was a statistically significant reduction
in the postoperative edema in those patients given
methyprednisolone at both 24 and 48 h. There was
some reduction in postoperative edema associated with
an increase in dose from 40 to 125 mg, although this
finding was not statistically significant. Minimal edema
still developed in the cases that used steroids.
Braxendale et al.31 gave patients 8 mg dexametha-
sone or placebo orally 2 h before surgery. Patients in
the dexamethasone group had significantly lower pain
scores 4 h after surgery than the placebo group. There
was no significant difference between the groups on the
first postoperative morning. Pain was reported using a
visual analog scale.
Beirne and Hollander32 found a significant reduction
in pain and swelling, but not trismus, after the admin-
istration of 125 mg methylprednisolone administered
intravenously. Swelling was measured using photo-
graphic and face-bow techniques. Pain was measured
by the number of pain pills that the patient reported
being used. The patients in the experimental group
reported less pain on the day of surgery than the control
group. On the day after surgery there was no statisti-
cally significant difference between the pain reports in
the 2 groups. The patients in the experimental group
used significantly less medication on the day of surgery
than the control group, but the 2 groups showed no
significant differences in the total number of pain pills
OOOOE
May 2009
taken after surgery. Facial swelling was significantly
reduced in the experimental group when measured by
the photographic and face-bow techniques on the day
following surgery. The experimental group had an in-
crease in swelling on the second and third days of
surgery, but this remained less than the swelling in the
control group.
Schmelzeisen and Frolich33 in 1992 investigated the
use of 6 mg dexamethasone given orally once 12 h
before and once 12 h after osteotomy of 2 impacted
third molar teeth. On the first day after surgery the
difference in cheek swelling was 54.3% as measured by
tape, 46% measured with a gauge, and 29% measured
by sonographic measurement of the cheek diameter in
the first molar area. Limitation in jaw opening was
reduced in the experimental group by 17.7%. Pain as
assessed by visual analog scale was reduction by about
50% in the dexamethasone group. The amount of an-
algesics required after surgery was reduced by 37%
with dexamethasone administration. The effect of the
drug was most pronounced on the first postoperative
day, when most of the swelling occurs, and the effect
was less obvious as the swelling subsided.
Skjelbred and Lokken34 injected 9 mg betametha-
sone intramuscularly. Patients were evaluated on the
third and sixth postoperative days, with a reduction in
swelling of 55% and 69%, respectively. Measurements
were made using a mechanical device. Pain assess-
ments made with a visual analog scale were signifi-
cantly lower in the steroid group.
Neupert et al.35 evaluated the use of 4 mg dexameth-
asone given intravenously in 60 patients. No differ-
ences in swelling and daily pain were noted, but trismus
and global pain were significantly affected by the ste-
roid. This study may have used a subtherapeutic dose,
and the method used to measure swelling may lack
sensitivity.
Schaberg et al.36 evaluated the effectiveness of meth-
ylprednisolone for the reduction of postoperative facial
edema in 39 patients who underwent either a Le Fort I
osteotomy or a transoral vertical osteotomy. Patients
were evaluated by computerized tomographic examina-
tion performed preoperatively and at 24 and 72 h after
surgery. Le Fort I osteotomy patients receiving meth-
ylprednisolone had a reduction in facial edema by 61%
at 24 h after surgery, and 10% at 72 h postoperatively.
Patients undergoing transoral vertical osteotomy had a
reduction in facial edema by 38% at 24 h and 45% at
72 h after surgery.
In a prospective, randomized, controlled, double-
blind study of 61 patients, Dionne et al.41 demonstrated
that preoperative dosing of dexamethasone in the third
molar oral surgery model reduced inflammation during
the postoperative period but was insufficient as an
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Volume 107, Number 5 Kim et al. 637

Table III. Summary of results of several studies that have investigated the use of corticosteroids before and after oral
surgical procedures
No. of
Reference patients Type of surgery Treatment administered Results
30 129 Removal of bilateral 1. Placebo (n ⫽ 44). Reduction in postoperative edema in those patients given MP
impacted third 2. MP 40 mg (n ⫽ 42). (P ⬍ .005 at both 24 and 48 h after surgery). There was
molars 3. MP 125 mg (n ⫽ 43). some reduction in postoperative edema associated with an
IV immediately before increase in dose, but this was not statistically significant.
surgery. There was an insignificant difference between the 3 groups
at 7 days.
37 47 Removal of bilateral 1.2 mg BM PO on the evening Patients served as their own control group. The control group
impacted third before surgery and then 1.2 mg had 5.6 times as much edema as the BM group, and there
molars PO QID to a total of 14.4 mg. was a significant reduction in the requirement for pain
medication in the BM group and less than one-half the
amount of trismus in the BM group compared with the
control. 4% of the BM group developed alveolar osteitis.
33 40 Removal of bilateral 6 mg DM PO 12 hrs before Patients served as their own control group. Decrease in
impacted third surgery and 6 mg DM PO 12 h cheek swelling compared with control at 24 h was 54.3%
molars after surgery. (P ⬍ .001) as measured by tape, 46% (P ⬍ .001) by a
gauge in the first molar area, and 29% (P ⱕ .056) by
sonographic measurement of cheek diameter. Limitation of
jaw opening was reduced by 17.7% (P ⬍ .002) after DM.
Pain assessed by visual analog scale was reduced by 50%
by DM (P ⬍ .01). 76% of patients preferred perioperative
DM over the control.
31 49 Removal of bilateral 1. 8 mg DM PO. Pain scores after 4 h were significantly lower in the DM
impacted third 2. Placebo. group (P ⬍ .005). There was no significant difference
molars Medication was between the groups on the first postoperative morning.
administered 2 h before Significantly more patients had severe swelling and
surgery. significantly fewer patients had mild swelling in the
placebo group compared with DM (P ⬍ .05). The %
reduction in mouth opening was similar in both groups.
34 24 Removal of bilateral 9 mg BM IM before surgery. Patients served as their own control group. The mean
impacted third reduction in swelling on the third and sixth postoperative
molars days was 55% (P ⬍ .001) and 69% (P ⬍ .001),
respectively. The mean reduction in mouth opening ability
from the preoperative state was 44% after placebo and
23% after active drug (P ⬍ 0.001). Pain assessments were
lower after the corticosteroid injection.
38 12 Removal of bilateral 9 mg BM IM 3 h after surgery Patients served as their own control group. The mean
impacted third reduction in swelling on the third and sixth postoperative
molars days was 47% and 14%, respectively. The mean reduction
in mouth opening on the third postoperative day was 46%
after placebo and 18% after active drug.
35 60 Removal of bilateral 4 mg DM IV before surgery. Patients served as their own control group. No differences in
impacted third swelling and daily pain. Trismus and global pain were
molars significantly altered in the steroid group.
39 11 Removal of bilateral 16 mg MP PO evening before Patients served as their own control group. Swelling was
impacted third surgery and 20 mg MP IV reduced by 42% at 24 h and 34% at 48 h after surgery. By
molars before surgery. the third day the difference was only 19%. Trismus or the
need for analgesic medication was not affected by this
dose of MP.
32 31 Removal of bilateral 1. 125 mg MP IV. Patients were assigned randomly to 2 treatment groups. One
impacted third 2. Placebo IV. day after surgery, the MP group reported significantly less
molars Medications were pain than the control group (P ⬍ .05). The MP group had
administered before surgery. significantly less swelling than the control group.

analgesic. It was shown, however, that postoperative and inflammation. This study used probes to quantify
administration of intravenous ketorolac suppressed the and measure levels of inflammatory markers at the sites
pain response and was effective in reducing both pain of tissue injury (lower third molar extraction sites).

638 Kim et al.
Table III. Continued
No. of
Reference patients Type of surgery Treatment administered
41 61 Removal of bilateral 1. 8 mg DM PO and IV before
impacted third surgery/placebo at pain
molars onset.
2. 8 mg DM PO and IV before
surgery/30 mg ketorolac at
pain onset.
3. Placebo before
surgery/placebo at pain
onset.
DM, Dexamethasone; MP, methylprednisolone; BM, metamethasone.
They showed that PGE2 and TXB2 levels were both
reduced in the patients treated with ketorolac, but only
TXB2 levels were reduced in the dexamethasone
group. They postulated that PGE2, the primary prosta-
noid responsible for the peripheral pain response, was
not suppressed adequately by dexamethasone to pre-
vent the sensitization of peripheral nociceptors. Fur-
thermore, the investigators proposed that dexametha-
sone inhibits COX-1 associated with TXB2 production
in certain cell types and has little effect on inhibiting
COX-1 PGE2 production in other cell types. Ketorolac
suppressing peripheral PGE2 levels and pain greater
than dexamethasone also may indicate that PGE2 levels
may need to be reduced below a certain critical level
before analgesia can be produced.41
RECOMMENDATIONS FOR THE APPROPRIATE
USE OF CORTICOSTEROIDS FOLLOWING
DENTOALVEOLAR SURGERY
There are several synthetic analogues of glucocorti-
coids available to the practitioner. The drugs vary in
their glucocorticoid potency, relative mineralocorticoid
potency, duration of action, and plasma half-life. Refer
to Table IV for a comparison of the most commonly
used agents. Plasma half-lives of the various synthetic
glucocorticoids vary from 1 h to approximately 4 h.
However, plasma half-life is not a good indication of
the duration of biologic activity of each steroid. Dura-
tion of action is best reflected in the period of adreno-
corticotropic hormone suppression by the pituitary
gland after the administration of a single dose of glu-
cocorticoids. The glucocorticoid potency of hydrocor-
tisone is very similar to the naturally occurring cortisol,
whereas methylprednisolone and dexamethasone are 4
to 20 times more potent, respectively.
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May 2009
Results
Patients were assigned randomly to 3 treatment groups.
Tissue samples collected at 20 min postoperative intervals
on buccal aspects of lower third molar extraction sockets
yielded decreased levels of TXB2 in DM treatment groups
compared with placebo. Group 2 showed significant
decrease in both TXB2 and PGE2 levels in the first 60
min after ketorolac administration compared with groups 1
and 3. Average time for requesting postoperative analgesic
was 119.3 min. No difference in time to pain onset among
all 3 groups. Pain intensity was similar in all 3 groups in
the immediate postoperative period. Administration of
ketorolac in group 2 patients resulted in a rapid analgesic
response with an analgesic effect being statistically
significant compared with groups 1 and 3 (P ⬍ .01).
Common preparations
Steroids for dentoalveolar surgery are available for
oral, parenteral, and intramuscular (IM) use. The most
commonly used agents are oral dexamethasone (Dec-
adron) and intravenous (IV) or IM dexamethasone so-
dium phosphate (Decadron Phosphate). Dexametha-
sone acetate, a longer-acting IM preparation, is also
available. A 0.75 mg dose of dexamethasone is equiv-
alent to 20 mg cortisol (hydrocortisone) and to 25 mg
cortisone. The biologic half-life of dexamethasone is
36-54 h, and it is considered to be a long-acting steroid.
Methylprednisolone is another commonly used cortico-
steroid in dentoalveolar surgery. It is available orally in
several strengths and is marketed under the trade name
Medrol. It can be used IM or IV as methylprednisolone
sodium succinate, and this is marketed as Solu-Medrol.
A longer-acting IM form, methylprednisolone acetate,
is available as Depo-Medrol. A 4 mg dose of methyl-
prednisolone is equivalent to 20 mg cortisol (hydrocor-
tisone) and to 25 mg cortisone. The biologic half-life of
methylprednislone is 18-36 h, and it is considered to be
an intermediate-acting steroid. Betamethasone, a long-
er-acting agent, is also available in oral, IM, and IV
preparations.23
DISCUSSION
The use of NSAIDs in managing oral surgical pa-
tients has been well described. From the literature
available, it is apparent that the combination of another
drug with an NSAID is often more effective in control-
ling postoperative pain and swelling in third molar
surgery than an NSAID alone. For example, the com-
bination of diclofenac and prednisolone offers a better
therapeutic outcome regarding pain and swelling, as
documented in various studies.18,20,21 It is important,
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Volume 107, Number 5
Table IV. Comparison of commonly used glucocorticoids
Equivalent glucocorticoid Mineralocorticoid potency
Drug potency (mg)
Cortisone 25
Hydrocortisone 20
Prednisone 5 0.25
Prednisolone 5 0.25
Methylprednisolone 4 0
Triamcinolone 4 0
Dexamethasone 0.75
Betamethasone 0.6
therefore, that combination drugs be recognized and
available to maximize the benefit of these antiinflam-
matory medications.
Most studies advocate the use of NSAIDs for pre-
venting postoperative pain,18,19 while glucocorticoids
for controlling postoperative swelling and tris-
mus.2,18,40 This is attributable to the role of prostaglan-
dins in local pain and the inhibition of these prostaglan-
dins in preventing the onset of pain. Glucocorticoids
exert their action at virtually every step in the inflam-
matory process, which leads to decreased capillary di-
latation, decreasing circulating lymphocytes, inhibiting
fibroblast proliferation, and inhibiting prostaglandins
and leukotrienes. The suppression of these factors ex-
erts a profound effect on tissue inflammation and thus
offers a potent therapeutic tool in managing patients
postoperatively.
Glucocorticoids are effective agents in reducing the
extent of the common postoperative sequelae of pain,
edema, and trismus after dentoalveolar surgery. To be
effective, these drugs must be given in adequate doses.
A dose of corticosteroids must equal or exceed the
physiologic amounts released by the body. Normal
daily output of cortisol is 15-25 mg/day, but up to 300
mg of cortisol can be released in a time of crisis. A dose
exceeding this limit would suppress the inflammatory
process to a greater extent than the body could by itself.
The authors of this paper suggest a dose equivalent to
300 mg cortisol for maximum effect. Doses of 125 mg
methylprednisolone, which is equivalent to 625 mg of
cortisol have been used in previous clinical trials with-
out adverse side effects.
Postoperative edema peaks 48-72 h after surgery.
Most glucocorticoids used in oral surgical procedures
do not exert their effect beyond 24 h if given as a single
dose. To maintain their antiinflammatory efficacy, ste-
roid doses should be maintained for a minimum of 3
days and a maximum of 5 days to maximize their
benefit and minimize their risk of causing delayed
healing and HPA axis suppression. The ideal route of
administration is intravenous. Steroids given through
Kim et al. 639
Duration of Plasma half-life
(relative) action (h) (min)
1 8-12 60
0.8 8-12 90
24-36 60
24-36 200
24-36 180
24-36 120
0 36-54 200
0 36-54 200
this route can provide an immediate pharmacologic
response, reduces patient noncompliance, and provides
a more predictable response. The oral route of admin-
istration gives a delayed onset of action, can create an
erratic response due to the pharmacokinetics of the
drug, and relies on patient compliance. However, the
oral route does provide a convenient, economic, and
safe route of administration of drug to most patients.
The intramuscular route of administration has a
slower onset of action than the intravenous route, and
the rate of absorption is highly dependent on the rate of
blood flow to the site of administration. The onset of
action is still faster than the oral route, and long-acting
depot preparations can be injected. Corticosteroids are
not indicated for routine use. Rather, they should be
used for more complex oral surgical procedure in which
trauma is categorized as moderate to severe. Oral sur-
gical procedures involving the removal of at least 1
partial bony or full bony impacted third molar tooth
falls into this category, as do long surgical procedures
which create a considerable amount of soft and hard
tissue trauma.
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Reprint requests:
Dr. King Kim
Oral and Maxillofacial Surgery
Oral and Facial Surgical Center/Baptist Memorial Golden Triangle
Hospital
300 Hospital Drive
Columbus, MS 39705
reykimes@yahoo.com