JOURNALOF ENDODONTICS
Copyright © 1999 by The American Association of Endodontists
Comparison of Effect of Intracanal Use of Ketorolac
Tromethamine and Dexamethasone with Oral
Ibuprofen on Post Treatment Endodontic Pain
Martin J. Rogers, DDS, Bradford R. Johnson, DDS, Nijole A. Remeikis, DDS, and Ellen A. BeGole, PhD
The purpose of this study was to compare the
pain-reducing efficacy of dexamethasone and ke-
torolac tromethamine when used as an intracanal
medication, with oral ibuprofen and a placebo. An
additional objective was to establish if any relation-
ship exists between the incidence and severity of
pretreatment pain and the incidence and severity
of postinstrumentation pain. A total of 48 patients
who presented to the University of Illinois post-
graduate endodontic clinic were invited to partici-
pate. Patients were randomly assigned to 1 of 4
groups: oral ibuprofen, placebo, dexamethasone,
or ketorolac tromethamine. Patients were asked to
evaluate their pretreatment pain when they pre-
sented to the clinic with a Visual Analog Scale. The
root canal treatment was performed in two ap-
pointments. The first appointment consisted of
cleansing and shaping of the canal/s and place-
ment of an intracanal medication. All teeth were
closed with a sterile cotton pellet and IRM. Each
patient was sent home with a Visual Analog Scale
to fill out at 6, 12, 24 and 48 h after initiation of
therapy. At the 12-h period, both dexamethasone
and ketorolac provided statistically significant bet-
ter pain relief than placebo. At the 24-h period, only
ketorolac demonstrated better pain relief than the
placebo. There were no statistically significant dif-
ferences among the groups at 6 and 48 h. Although
ibuprofen pain ratings were less than the placebo
at all time points, the reduction was not significant.
In addition, no significant differences were demon-
strated between ibuprofen and either dexametha-
sone or ketorolac.
Pain of endodontic origin can be a major concern to the patient and
the clinician. Public perception of endodontic treatment is often
associated with pain. Expectations of a painful experience can
increase a patient's anxiety level making treatment more difficult.
381
Printed in U.S.A.
VOL. 25, NO. 5, MAY 1999
The use of intravenous sedation, nitrous oxide sedation, adequate
local anesthesia, and oral anxiolytic agents can aid in relaxing the
patient and making the procedure less threatening.
Pain between appointments is sometimes an unavoidable se-
quela to endodontic treatment. Many authors have evaluated the
incidence of interappointment pain. Seltzer et al. (1) reported that
40% of 698 patients experienced some degree of pain after root
canal therapy. In a study of 318 patients, Clem (2) found a 25%
incidence of moderate to severe pain after the instrumentation
appointment. O'Keefe (3) found that 16% of his patients had
moderate to severe pain either during or after treatment visits. He
also found that there is a strong relationship between preoperative
and postoperative pain. Patients with moderate to severe pain prior
to treatment were five times more likely to experience moderate to
severe pain posttreatment.
Penniston and Hargreaves (4) evaluated the efficacy of ketoro-
lac tromethamine after intraoral submucosal injection. They
showed that ketorolac is an effective analgesic after the intraoral
injection. There were no clinically evident signs of adverse effects
or tissue toxicity at the end of their study. Negm (5) studied the use
of two nonsteroidal anti-inflammatory agents (diclofenac and ke-
toprofen) with and without the use of hyaluronidase to control
posttreatment pain. The study medications were placed with a
16-gauge needle that went into the canal until resistance was felt;
then 0.1 ml of the medication solution was expressed slowly in
each canal. The results indicated that this method of use for
diclofenac and ketoprofen was effective in controlling posttreat-
ment pain (5). Ketorolac tromethamine can also be found in oph-
thalmic solutions for the relief of ocular itching due to seasonal
allergic conjunctivitis.
The purpose of this study was to compare the efficacy of
dexamethasone and ketorolac tromethamine when used intracanal
under gentle pressure to oral ibuprofen and placebo in controlling
postinstrumentation pain.
M A T E R I A L S AND M E T H O D S
Patients who presented to the University of Illinois postgraduate
endodontic clinic were evaluated for this study, and a total of 48
patients participated. A complete medical history of all patients
was taken. Only those patients who had no significant medical
382 Rogers et al. Journal of Endodontics

TABLE 1. Adjusted pain ratings

Actual 6H 12 H* 24 H I 48 H
pre Actual Adjusted Actual Adjusted Actual Adjusted Actual Adjusted
Ibuprofen 28.4 28.2 28.8 21.7 22.1 12.4 12.5 9.8 9.9
Placebo 23.6 36.3 39.4 26.6 28.3 17.6 18.3 14.3 15.1
Dexamethasone 43.2 32.8 26.1 17.5 13.9 8.3 6.8 6.4 4.8
Ketorolac 23.9 26.2 29.t 12.5 14.1 2.8 3.5 1.8 2.5
* p < 0.05: placebo differs from dexamethasone and ketorolac.
1 P < 0.05: placebo differs from ketarolac.

problems and met the following criteria were considered for the
study:
1. Between 18 and 65 years of age
2. Not pregnant or nursing
3. No history of peptic ulcer or gastrointestinal bleeding
4. Not hypersensitive or allergic to nonsteroidal anti-inflamma-
tory drugs (NSAIDs) or corticosteroids
5. Not at risk for renal failure or renal impairment
6. No radiographic evidence of periapical pathosis.
Only patients with a vital pulp (either diagnosed as an irrevers-
ible pulpitis or normal, but in need of endodontic therapy), as
determined by an electric pulp tester (Analytic Technology, Red-
mond WA) and thermal testing, were included in the study. If the
patient met all of the above criteria, he/she was informed of the
study and invited to participate. He/she was asked to read and sign
a consent form approved by the Institutional Review Board at the
University of Illinois at Chicago. Patients were randomly assigned
into 1 of 4 groups:
1. Oral ibuprofen
2. Placebo
3. Dexamethasone
4. Ketorolac tromethamine.
The root canal treatment was performed in two appointments.
The first appointment consisted of cleansing and shaping of the
canal/s, using standard aseptic technique. If the tooth could not be
properly accessed, a canal could not be located, or swelling de-
veloped the patient was excluded from the study. The RCT pro-
cedure was conducted utilizing a crown-down technique. The
canals were enlarged to minimum size of a #25 file or larger,
depending on the size of the canal. Sodium hypochlorite (2.6%)
was used as an irrigant, and the cleansing and shaping were
conducted in the presence of RC-prep (Premier Dental Products
Co., Philadelphia, PA). After complete cleansing and shaping, the
canals were dried in groups 3 and 4, and either dexamethasone or
ketorolac tromethamine was placed intracanal. The method of
placement was as follows: a 27-gauge needle was placed into the
canal until resistance was felt, then 0.1 ml of the medication
solution was expressed slowly into each canal. The two solutions
were ketorolac tromethamine (60 rag/2 ml) and dexamethasone (4
mg/ml). Patients in the other two groups received either oral
ibuprofen (600 rag) or oral placebo and no intracanal medicine. All
teeth were closed with a sterile cotton pellet and IRM (Intermediate
Restorative Material, L. D. Caulk Division, Dentsply International,
Milford, DE).
The patients were asked to evaluate their pretreatment pain
when they presented to the clinic with a Visual Analog Scale
(VAS) to determine if any relationship would be found to exist
between pretreatment and posttreatment pain. Each patient was
dismissed with a VAS to fill out at 6, 12, 24, and 48 h after
initiation of therapy. Because the patients were allowed to take
over-the-counter medication during the study, they were asked to
BI~ 12hm ~,hm 48hm
FiG 1. Group means of pain level adjusted for pretreatment pain as
covariate for the time periods (larger numbers indicate more severe
pain). Dexameth, dexamethasone.
indicate on the scale what type of medication and when they took
it on the VAS.
The scale contained a mark at the center of each word desig-
nation. At the midpoint between the marks, boundaries for each of
the categories were established so that each pain levels designation
had a possible range of values in order to accommodate patients
who marked the scale between the marks. In addition, for the sake
of statistical analysis, the scale was converted to a continuous scale
by measuring where the patient designation of pain was in relation
to the 0 point on the scale. The original scale was 150 mm in
length, and it was standardized so that the final scale measured 100
ram, the usual length of a VAS scale. The final scale was as
follows:
None: 0 - 6 . 0
Faint: >6.0-17.0
Weak: > 17.0-27.0
Mild: >27.0-42.3
Moderate: >42.3-60.3
Strong: >60.3-74.7
Intense: >74.7-90.6
Maximum: >90.6-100
RESULTS
An analysis of covariance, as shown in Table l, was performed
using pretreatment pain as a covariate to adjust for differences in
initial pain. Figure 1 demonstrates the differences found among
groups. Both dexamethasone and ketorolac showed statistically
significant relief in pain at the 12-h time periods, compared with
Vol. 95, No. 5, May 1999
TABLE 2. Frequency of over-the-counter medication use after
the first appointment
Supplemental No Supplemental
Drug Medication Medication Total
Ibuprofen 3 9 12
Placebo 6 6 12
Dexam~hasone 2 10 12
Ketorolac 1 11 12
Total 12 36 48
X2 - 6.2, p < 0.10.
the placebo. Ketorolac demonstrated statistically significant pain
relief over the placebo at the 24-h time period. Although ibuprofen
pain ratings were less than the placebo at all time points, the
reduction was not significant. There was no significant difference
among the groups at 6 or 48 h. In addition, no significant differ-
ences were demonstrated between ibuprofen and either dexameth-
asone or ketorolac. Patients were allowed to take over-the-counter
pain medication. Frequency of taking the over-the-counter pain
medication was not statistically significant among the groups. As
shown in Table 2, it was found that of the patients requiring
supplemental medication:
Group 1:3/12 (25%) needed supplemental medication at ap-
proximately 6 to 8 h
Group 2:6/12 (50%) needed supplemental medication between
6 to 35 h
Group 3:2/12 (16.7%) needed supplemental medication at ap-
proximately 6 to 12 h
Group 4:1/12 (8.3%) needed supplemental medication at ap-
proximately 6 to 8 h
Table 3 demonstrates the intensity of pain patients felt within
the four groups.
DISCUSSION
Ketorolac tromethamine is the first and only NSAID that is
available in an injectable formulation in the United States. It is a
member of the pyrrolo-pyrrole group, and its primary mode of
action is the inhibition of the cyclo-oxygenase pathway that me-
tabolizes arachidonic acid to prostaglandins and thromboxanes. It
has been shown to be extremely effective for pain reduction from
a variety of etiologies, such as oral surgery, cancer, and migraine
headaches.
Prostaglandins play a role in the induction of inflammation,
lowering the pain threshold, and sensitizing nociceptors to other
pain mediators, such as histamine and bradykinin. Ketorolac
tromethamine acts by inhibiting the production of prostaglandins
through the inhibition of cyclo-oxygenase. This provides the ra-
tionale for the efficacy of ketorolac tromethamine as an analgesic
for the relief of odontogenic pain. Pulpal inflammation and necro-
sis are known to cause the release of chemical mediators, including
prostaglandins, which are involved in the mediation of pain. Plac-
ing the drug directly at the site of tissue injury may be more
effective in controlling pain and inflammation than waiting for
absorption through the gastrointestinal tract. This method of place-
ment could give practitioners another option for pain control in
endodontics. NSAIDs have been shown to be effective in the relief
of posttreatment pain by many investigators (6-9).
Intracanai Use of Ketorolac 383
It has been suggested that antibiotics must be given in conjunc-
tion with steroids to prevent secondary infection. The implication
is that suppression of inflammation also means a decrease in local
defenses permitting proliferation of pathogenic microorganisms
(10). We found no evidence of this phenomenon in our study. No
patients reported fever, malaise, or any fluctuant swellings after the
administration of dexamethasone. Therefore, the routine use of
antibiotics in conjunction with intracanal steroids may not be
necessary.
In the present study, two patients experienced a flare-up. One
flare-up was from the placebo group, and the other was from the
ketorolac tromethamine group. Both required an intra-appointment
visit. The flare-up from the patient in the placebo group showed no
signs of swelling, but caused extreme pain. Upon opening the
tooth, purulent drainage was established. The tooth was irrigated
with 5.25% NaOC1, dried, and then sealed with IRM. The patient
was given Penicillin VK 500 mg qid for 7 days and a hydrocodone
combination drug for pain. The flare-up from the patient in the
ketorolac tromethamine group also presented complaining of ex-
treme pain, but without swelling. Upon opening the tooth, no
drainage could be established; the canals were dry. The tooth was
irrigated with 5.25% NaOC1, dried, then sealed with Cavit. The
patient was given a hydrocodone combination drug only. The
patient stated she felt better later that day.
The patients that participated in this study were permitted to
take over-the-counter medications if needed, without being ex-
cluded from the study. We felt this was a more realistic approach
to postinstrumentation pain, because we know that patients will be
taking over-the-counter medications. If over-the-counter pain med-
ications were utilized, we obtained an accurate history of the time
interval after treatment that pain medications were needed.
There was a statistically significant difference found among the
groups at 2 time periods when comparing pain relief using analysis
of covariance. The frequency with which the patients needed
supplemental medication may have played a role in the scores on
the VAS. However, the frequencies were not statistically signifi-
cant among the groups. Thus, it is possible that taking over-the-
counter medication affected the groups equally. This information
could become useful in determining how patients tend to take
medications, what type of medication they take for their pain, and
what is the most effective pain medication for pain.
After the start of our study, the Roche Laboratory issued the
following warning: "Toradol, a nonsteroidal anti-inflammatory
drug, is indicated for the short-term (up to 5 days) management of
moderately severe, acute pain, that requires analgesia at the opioid
level. It is not indicated for minor or chronic painful conditions.
Increasing the dose of Toradol beyond the label recommendations
will not provide better efficiency but will result in increasing the
risk of developing serious side effects." The warning that was
issued resulted from a review of a large postmarketing surveillance
study of approximately 10,000 patients and adverse event reports.
In many of these cases, the Food and Drug Administration and
Syntex noted inappropriate use of Torado] that resulted in serious
adverse events.
In our study, there were no noted adverse side effects from the
use of Toradol when used as an intracanal medicine. Penniston and
Hargreaves (4) injected ketorolac tromethamine periapically and
noted no adverse effects or tissue toxicity in any of their subjects.
It would appear that the use of ketorolac tromethamine at the doses
available in the methods described herein is a safe method of
delivery.
It was interesting to note that, when the solutions of either
384 Rogers et al. Journal of Endodontics

TABLE 3. Reported frequencies of pain levels

None Faint Weak Mild Moderate Strong Intense Maximum Total

Ibupmfen 26 10 8 6 2 8 0 0 60
Placebo 13 4 10 19 6 6 0 2 60
Dexamethasone 32 2 4 8 7 2 3 2 60
Ketorolac 35 5 6 9 2 2 1 0 60

Total 106 21 28 42 17 18 4 4 240

ketorolac tromethamine or dexamethasone were injected into the
canals as described, the majority of the 0.1 mt was expressed back
out of the canal into the chamber. Negm (6) incorporated hyal-
uronidase into the solution of the NSAIDs, ketoprofen and diclofe-
nac; and, although he stated that more patients were pain-free when
the combination was used, there was no statistically significant
difference.
The intracanal use of ketorolac tromethamine or dexamethasone
provided statistically significant pain relief at the 12-h time period,
compared with placebo. Ketorolac tromethamine also provided
statistically significant pain relief at the 24-h time period, com-
pared with placebo. However, although ibuprofen pain ratings
were less than the placebo at all time points, the reduction was not
significant. In addition, no significant differences were demon-
strated between ibuprofen and either dexamethasone or ketorolac.
Therefore, the same reduction in pain could potentially be achieved
through the use of ibuprofen. Future research should help quantify
how much of the drug is actually reaching the periapical region and
whether or not the addition of other agents, such as hyaluronidase,
would be beneficial.
This research was supported in part by a grant from the AAE Research and
Education Foundation.
The authors would like to thank Dr. Kenneth M. Hargreaves, DDS, PhD, for
his valuable assistance with this project.
Brs. Rogers, Johnson, and Remeikis are affiliated with the Department of
Endodontics and Dr. BeGole is affiliated with the Department of Orthodontics
at the University of Illinois at Chicago College of Dentistry, Chicago, IL.
Address requests for reprints to Martin J. Rogers, DDS, Department of End-
odontics (M/C 642), College of Dentistry, 801 South Paulina, Chicago, IL
60612.
References
1. Seltzer S, Bender IB, Ehrenrich J. Incidence and duration of pain fol-
lowing endodontic therapy: relationship to treatment with sulfonamide and to
other factors. Oral Surg Oral Med Oral Pathol 1961;14:74-82.
2. Clem WH. Post-treatment endodontic pain. J Am Dent Assoc 1970;81:
1166-70.
3. O'Keefe EM. Pain in endodontic therapy: preliminary study. J Endodon
1976;2:315-9.
4. Penniston S, Hargreaves K. Evaluation of periapical injection of ketoro-
lac for management of endodontic pain. J Endodon 1996;22:55-9.
5. Negm M. Effect of intracanal use of nonsteroidal anti-inflammatory
agents on posttreatment endodontic pain. Oral Surg Oral Med Oral Pathot
1994;77:507-13.
6. Negm M. Management of endodontic pain with nonsteroidal anti-ira
flammatory agents: a double-blind, placebo-controlled study. Oral Surg Oral
Med Oral Patho11989;67:88-95.
7. Torabinejad M, Dorn S, Eleazer P, Frankson M, Jouhari B, Mullin R,
Soluti A. Effectiveness of various medications on postoperative pain following
root canal obturation. J Endodon 1994;20:427-31.
8. Forbes J, Kehm C, Grodin C, Beaver W. Evaluation of ketorolac, acet-
aminophen, and an acetaminophen-codeine combination in postoperative
oral surgery pain. Pharmacotherapy 1990;10(part 2):94s-105s.
9. Brown C, Moodie J, Wild V, Bynum L. Comparison of intravenous
ketorolac tromethamine and morphine sulfate in the treatment of postopera-
tive pain. Pharmacotherapy 1990; 10(part 2): 116s-121 s.
10. Van Cura JE, Remeikis NA. A corticostereid-antibiotic combination in
the treatment of acute secondary apical periodontitis. II. Dent J 1970;39:307-
12.