CLINICAL EBOOK SERIES

POWERED BY

INNOVATIONS IN
DENTAL PAIN
MANAGEMENT
APRIL 2020

2 C E C R E D I T S

PRESCRIPTION ANALGESIA

Prescribing Analgesics
for Postoperative Dental Pain
Mana Saraghi, DMD; Elliot V. Hersh, DMD, MS, PhD;
Victor M. Badner, DMD, MPH; and Nadia Laniado, DDS, MPH

2 C E C R E D I T S

INTRANASAL KETOROLAC

Characterization and Treatment of

Postsurgical Dental Implant Pain
Employing Intranasal Ketorolac
Rebecca Bockow, DDS, MS; Jonathan Korostoff, DMD, PhD; Andres Pinto, DMD,
MPH; Matthew Hutcheson, MS; Stacey A. Secreto, CRC; Laura Bodner, DMD; and
Elliot V. Hersh, DMD, MS, PhD

SUPPORTED BY AN UNRESTRICTED GRANT FROM UNITED CONCORDIA DENTAL • Published by AEGIS Publications, LLC © 2020
 Helping Patients
Ease the Pain
of Continuing Education in Dentistry

D
APRIL 2020 | www.compendiumlive.com

PUBLISHER
Matthew T. Ingram
of Continuing Education in Dentistry
SPECIAL PROJECTS DIRECTOR
entistry is more than performing proce- C. Justin Romano
dures. A crucial aspect of the dental pro- SPECIAL PROJECTS EDITOR
Cindy Spielvogel
fession that may not get the attention of a of Continuing Education in Dentistry
SPECIAL PROJECTS COORDINATOR
novel technique or a new, innovative ap- June Portnoy

proach is the management of patient pain. BRAND COORDINATOR

Perri Lerner
As dentists, we need to treat this aspect of patient care with MANAGING EDITOR
equal consideration and give it our utmost respect. Bill Noone

This special eBook from Compendium focuses on this im- CREATIVE

Claire Novo
portant topic, featuring two thoroughly informative articles. EBOOK DESIGN
The first, a continuing education (CE) article, addresses the Jennifer Barlow

role prescription analgesics in dentistry plays in the opioid
crisis in the United States, and how to mitigate the need for
opioids post-treatment by using a multimodal analgesic ap-
proach. This allows for the use of medication in different drug
classes to intercept pain at various points.
With the rise in use of dental implants, pain management is
critical. New solutions in patient-friendly pain management
are being explored. The second CE describes an intranasal
ketorolac medication that offers patients a convenient drug
that they can self-administer. The study conducted shows a
rapid analgesic onset among participants, which resulted in
enhancing patient comfort and reducing the chance of exces-
sive drug dosing.
We strive to keep our patients as comfortable as possible.
Therefore, it is important for dentists to be ever diligent in
assisting patients’ progress through dental procedures, all the
way through completion of healing. This eBook is intended to
offer ideas on how to succeed in this endeavor. For additional
Copyright © 2020 by AEGIS Publications, LLC. All
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Chairman
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Vice Chairman
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resources on management of dental pain, please visit https:// Corporate Associate

Jeffrey E. Gordon
www.aegisdentalnetwork.com/cced/pain-management/. Media Consultant, East
Scott MacDonald
Subscription and CE information
Sincerely, Hilary Noden
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2 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 1 PRESCRIPTION ANALGESIA

Prescribing Analgesics for

Postoperative Dental Pain
Mana Saraghi, DMD; Elliot V. Hersh, DMD, MS, PhD; Victor M. Badner, DMD, MPH; and Nadia Laniado, DDS, MPH

ABSTRACT: It is well-known that there is an opioid crisis in the United States. Prescription
opioid analgesics contribute to this crisis; in 2012, dentists ranked second to physicians as
the top prescribers. The medical and dental literature demonstrates that dental prescribing
practices have been excessive, resulting in leftover medication that could then be diverted,
misused, or abused. A multimodal analgesic approach is highly valuable in targeting pain
along various points on the peripheral and central pain pathways and includes the use of
long-acting local anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), acetamino-
phen, and opioids, the last of which are generally reserved for the most severe pain only. The
Dental Impaction Pain Model demonstrates that NSAIDs are the frontline drugs for postop-
erative dental pain. Opioids have their role in postoperative analgesia but should be reserved
for severe breakthrough pain or in situations where NSAIDs may be contraindicated.

LEARNING OBJECTIVES

•Describe the contribution •Discuss the evidence •Discuss the role of

of past dental prescribing supporting NSAIDs as the acetaminophen, long-acting
practices to the opioid crisis. first-line medication for the local anesthetics, and opioids
treatment of postoperative in the management of
dental pain. postoperative dental pain, in

I
addition to NSAIDs.

n 2014, Americans were one and a
half times more likely to die from an
opioid overdose than from a motor ve-
hicle crash.1 The ongoing misuse and
abuse of highly addictive prescription
opioids has led to a public health crisis in the
United States. Since 2000, there has been
a 200% increase in opioid overdose deaths
due to prescription opioid analgesics and
heroin. In 2014, 61% of drug overdose deaths
were attributable solely to opioids.1 In 2016,
healthcare providers wrote more than 214
million prescriptions for opioid pain medi-
cation, a rate of 66.5 prescriptions per 100
people. In 2018, the government declared
a public health emergency and allocated
part of a $1.3 trillion spending bill to com-
bat the opioid addiction epidemic, which is
estimated to have a total economic burden
of $78.5 billion per year, including the costs
of healthcare, lost productivity, addiction
treatment, and criminal justice involvement.2
The Opioid Epidemic
The factors contributing to this crisis are var-
ied, although the beginning of the epidemic can
be traced to OxyContin®, a sustained-release
formulation of oxycodone manufactured by
Purdue Pharma,3 a drug that was not commonly
prescribed by dental professionals. Aggressive
marketing of opioid pain medications promoting
their effectiveness while de-emphasizing their

3 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 1
addictive potential was a major contributor to
overprescribing by clinicians. In 2001, the Joint
Commission’s Pain Management Standards led
to the popularization of pain as “the 5th vital
sign,” and what followed were efforts to treat
acute pain as aggressively as possible.4 Some
providers may have had noble intentions to
prevent any pain or discomfort for patients, but
they may have overestimated the magnitude of
patients’ postoperative pain; others cited con-
cerns for patient satisfaction and online prac-
tice reviews as justification for their prescribing
practices.4 Nevertheless, these ensuing prescrib-
ing practices contributed to an increase in opioid
exposure and an increased amount of leftover
medication that could be misused, abused, or
diverted to others.5 Efforts are currently under
way to minimize the use of opioid analgesics for
acute pain.6 Many major opioid distributors and
manufacturers now face criminal investigation
from dozens of states, cities, and counties with
regard to their misrepresentation of the safety
and efficacy of opioids. In addition to the culture
of overprescribing, other factors contributing
to the epidemic include “doctor shopping” and
prescription fraud.
Opioid Prescribing Practices
in Dentistry
Dental prescribers are unique because the
management of acute postoperative pain is a
central component of their practices. In 2012,
dentists prescribed 6.4% of the total opioid pre-
scriptions in the United States, second just to
primary care physicians.7,8 Although dentists do
not account for the largest number of prescrip-
tions, they are the top prescriber of opioids for
adolescents.9 Dentists were reported to write
approximately 31% of their immediate-release
opioid analgesic prescriptions (acetaminophen
plus codeine, hydrocodone, or oxycodone) for
youth aged 10 to 19 years, ages when dental
surgery for third-molar removal is prevalent.10
It has been estimated that there are approxi-
mately 5 million individuals, mostly young
4 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
adults and adolescents, in the United States
who undergo wisdom tooth extraction surgery
annually.11 The overprescribing of opioids has
significant implications for the developing
adolescent brain. It has been shown that the
prefrontal cortex is not completely developed
until age 20 to 25 years.12 A recent study found
that legitimate opioid use before high school
graduation is independently associated with a
33% increase in the risk of future opioid misuse
after high school.13
In a cross-sectional study of prescriptions
for opioids in 2016, dentists in the United
States were found to have prescribed four
times the amount of opioids as dentists in
England.14 The amount of prescription opioids
peaked in 2010 at 782 morphine milligram
equivalents (MME) per patient.15 Different
opioids have different potencies, or the dose
needed to produce a given effect or response.
Oral medications such as oxycodone 5 mg,
hydrocodone 10 mg, and codeine 60 mg are
all equivalent to oral morphine 10 mg, or are
said to be equal to 10 MME. The comparison
of MMEs adjusts for the potencies of differ-
ent opioids. Although prescription rates have
since been declining, it was observed that for
individuals with private health insurance, the
number of opioids prescribed by dentists in-
creased from 2010 to 2015, with the greatest
increase in prescriptions, as well as dosage, for
adolescents aged 11 to 18 years.7,16
Aside from ambulatory care visits in dental
offices, emergency departments (EDs) func-
tion as a venue for the receipt of opioid pre-
scriptions for nontraumatic dental conditions
(NTDCs) from physicians who are not familiar
with the diagnosis and management of dental
pain.17 Among adolescents and young adults
who visited EDs in 2005 and 2015, opioids
were prescribed for NTDCs at a rate of 59.7%
and 57.9% per visit, respectively.17 These num-
bers are significant because teens exposed to
oral opioids may be at increased risk of sub-
sequent fentanyl and heroin use.18 It has been
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 CONTINUING EDUCATION 1
“Dentists should consider nonsteroidal
anti-inflammatory analgesics as the first-line therapy
for acute pain management.”
estimated that one in eight deaths in teens and
young adults is linked to opioids.17
In dentistry, the most commonly prescribed
immediate-release opioid formulation is ac-
etaminophen with hydrocodone bitartrate
for surgical dental visits; formulations with
codeine and oxycodone are also prescribed
frequently.5 On average, 20 opioid pills are
prescribed after dental extractions; howev-
er, less than half of opioids prescribed after
surgical extractions are used.5 The unused
medications may lead to sharing and misuse
of these medications for nonmedical purposes.
Alarmingly, one-third of the opioid prescrip-
tions are for nonsurgical dental visits.5,7,19
Changing Guidelines
and Regulations
The recent decline in opioid prescribing is
due to a combination of state legislation, fed-
eral laws, Centers for Disease Control and
Prevention (CDC) reports, professional medi-
cal and dental organizations, continuing edu-
cation, and prescription drug monitoring pro-
grams (PDMPs).20,21 PDMPs are tasked with
collecting information about prescription data
on controlled substances, with the goal of reduc-
ing prescription drug abuse and identifying pa-
tients who are on excessive doses or dangerous
combinations of Drug Enforcement Association
scheduled drugs.22 Although they can be time-
consuming for the provider, these programs are
valuable in that they enable clinicians to identify
patients with a history of drug-seeking behavior
or a history of legitimate prescriptions for other
opioids, benzodiazepines, or barbiturates that,
if taken with an additional opioid prescription,
5 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
may result in potentially lethal central nervous
system or respiratory depression. Recent stud-
ies have shown that mandatory PDMPs caused
a 78% reduction in the quantity of opioids pre-
scribed and an increase in prescriptions for
non-opioid analgesics.23 In New York State, a
mandatory PDMP was instituted in 2014. It led
to a significant decrease in doctor shopping. One
study showed a 78% reduction in the quantity of
opioid pills prescribed in a dental urgent care
center.23 Currently all states except Missouri
have a mandatory PDMP.
In 2016, the American Dental Association
revised its statement on the use of opioids in
the treatment of dental pain.24 The revision
states: “Dentists should consider nonsteroidal
anti-inflammatory analgesics as the first-line
therapy for acute pain management.” Although
the official policy has changed, studies have
shown that clinical practice guidelines are
not effective in promoting behavioral change
among healthcare professionals.25 Bolstering
the guidelines with mandatory continuing
education has proven a vital and important
means of improving provider knowledge and
competency in opioid prescription manage-
ment.21 In addition, significant efforts in den-
tal schools toward educating new generations
of providers have been implemented, includ-
ing curriculum and clinical protocol changes.26
The Evidence Supports a
Multimodal Analgesic Approach
for Prescribing Analgesics for
Postoperative Dental Pain
Multimodal analgesia is a term that has received
increased attention due to the opioid crisis. It
www.compendiumlive.com
 CONTINUING EDUCATION 1 PRESCRIPTION ANALGESIA

means to intercept pain at multiple areas along
the peripheral and central pain pathways, result-
ing in an additive analgesic effect while reduc-
ing the doses and side effects of each drug class
utilized. It is an opioid-sparing strategy that at
most can result in prescriptions for a 2- to 3-day
course of opioids, as opposed to prescribing as
many as 30 pills.27 Dentists who render an area
anesthetized with local anesthetic and then pre-
scribe postoperative oral analgesics such as non-
steroidal anti-inflammatory drugs (NSAIDs),
acetaminophen, and opioids are already using
multimodal analgesic regimens.27-29
Despite their over-the-counter (OTC) sta-
tus, NSAIDs and acetaminophen can provide
at least equal to, if not superior, analgesia to
that of opioids for dental pain after removal of
impacted third molars.27,28 The role of opioids
in managing severe acute postoperative dental
pain is limited. First-line treatments include
profound long-acting postoperative local an-
esthesia, NSAIDs, and acetaminophen. Each
of these drug classes have their own indica-
tions, contraindications, adverse effects, and
drug-drug interactions of which the dental
provider must be aware. A detailed discus-
sion on the pharmacology of local anesthetics,
NSAIDs, and acetaminophen is outside of the
scope of this article.
Figure 1 illustrates the stepwise manner for
prescribing analgesics for acute postoperative
dental pain.27,28 Ibuprofen is the first-line drug

Fig 1. The stepwise guidelines for acute postoperative pain management in dentistry recommend that ibupro-
fen should be the frontline drug for all levels of pain, and acetaminophen should be added for more moder-
ate to severe pain, followed by opioids for the most severe breakthrough pain. Some major contraindications
to NSAIDs include a history of gastrointestinal bleeds, ulcers, and perforations; poor kidney function; taking
anticoagulants, and NSAID-sensitive asthma or allergy. If NSAIDs are contraindicated, the first-line drug should
be acetaminophen, with the addition of an opioid for more severe forms of pain. The maximum recommended
daily dose of acetaminophen is 4,000 mg; however, the manufacturers of Tylenol have reduced the maximum
recommended daily dose to 3,000 mg.30 Included in the column to the left are examples of dental procedures
that may produce mild, moderate, and severe pain.27,28

6 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 1
If NSAIDs are contraindicated,
the first-line medication
becomes acetaminophen.
for moderate to severe postoperative dental
pain. For mild pain, ibuprofen 200 to 400 mg
can be taken on an as-needed-for-pain basis
every 6 hours. As the pain escalates to mild
to moderate pain, ibuprofen 400 mg can be
taken on a fixed interval (around the clock)
every 4 hours for the first 24 hours, followed
by ibuprofen 400 mg every 4 hours on an as-
needed basis. For moderate to severe pain,
ibuprofen 400 mg plus acetaminophen 500
mg would be taken on a fixed interval every 6
hours for the first 48 hours, followed by ibu-
profen 400 mg every 4 hours as needed. For
severe pain, ibuprofen 400 mg plus an acet-
aminophen 650 mg plus hydrocodone 10 mg
combination would be taken every 6 hours
on a fixed basis for 48 hours, followed by ibu-
profen 400 mg and acetaminophen 500 mg
every 4 hours as needed. The maximum daily
dose for ibuprofen should not exceed 2,400
mg, and the maximum recommended daily
dose of acetaminophen should not exceed
4,000 mg.27,28 The maximum recommended
daily dose of Tylenol® (McNeil Consumer
Healthcare Division of Johnson & Johnson),
the brand-name formulation of acetamino-
phen, is 3,000 mg. Medical literature supports
the safety of the maximum recommended
daily dose of acetaminophen at 4,000 mg for
a short period. The manufacturers voluntarily
reduced the maximum recommended dose
because there are many combination drug
products that contain acetaminophen, includ-
ing not only opioid-acetaminophen combina-
tion prescription drugs but also OTC cold and
cough medications. The concern was that an
overdose and hepatotoxicity would occur if
7 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
an individual were unknowingly taking sev-
eral acetaminophen-containing products.30
Dentists should query patients about their
intake of such products and educate them
about the potential dangers of using multiple
products that contain acetaminophen.
If NSAIDs are contraindicated, the
first-line medication becomes acetamino-
phen. Acetaminophen is synonymous with
paracetamol and N-acetyl-para-aminophenol,
abbreviated as APAP. For mild pain, acetamin-
ophen 650 to 1,000 mg can be taken every 6
hours on an as-needed-for-pain basis. The
reason for many published guidelines stating
650 to 1,000 mg of acetaminophen is that the
available formulations of acetaminophen in-
clude 325 mg and 500 mg tablets, so two tab-
lets would be 650 mg or 1,000 mg, respectively.
Additionally, because the maximum recom-
mended dose for generic acetaminophen is
4 g (4,000 mg) per day, dosing of 1,000 mg
every 6 hours would be the maximum dose.
For moderate pain, acetaminophen 650 mg
plus hydrocodone 10 mg can be taken every 6
hours for a fixed interval for 24 hours. Then,
acetaminophen 650 to 1,000 mg can be taken
every 6 hours on an as-needed-for-pain basis.
For patients who cannot tolerate NSAIDs and
are experiencing severe pain, acetaminophen
650 mg plus hydrocodone 10 mg can be taken
every 6 hours for a fixed interval for 48 hours.
Then, acetaminophen 650 to 1,000 mg can be
taken every 6 hours on an as-needed-for-pain
basis. The maximum daily dose of acetamino-
phen should not exceed 4,000 mg.28
Other strategies to reduce pain include
preemptive analgesia and postoperative
www.compendiumlive.com
 CONTINUING EDUCATION 1 PRESCRIPTION ANALGESIA

long-acting local anesthetics. Preemptive

analgesia means taking analgesics before
the start of the procedure or postoperatively
before pain has arisen. Postoperative pain is
driven by a variety of inflammatory media-
tors, including prostaglandins. Administering
medication before an incision will limit the
production of prostaglandins from the outset
rather than after a procedure—or if taken im-
mediately after surgery, before the effects of
the local anesthetic have dissipated. The pre-
emptive administration is practical because
the patient may have limited ability to eat or
take oral medications postoperatively.31,32
The administration of the long-acting local
anesthetic 0.5% bupivacaine plus 1:200,000
epinephrine at the end of a procedure can re-
duce pain scores for up to 48 hours postopera-
tively. A reduction in postoperative pain will
result in less analgesic consumption, fewer
drug-specific side effects, and potentially less
exposure to opioids. In a study by Gordon et al
of patients who had their third molars removed
under general anesthesia, pain scores were
reduced for 48 hours if the long-acting local
anesthetic solution of 0.5% bupivacaine plus
1:200,000 epinephrine was administered im-
mediately postoperatively compared with pa- Fig 2. Administration of long-acting local anesthet-
tients who were not given this regimen (Figure ic, such as bupivacaine, significantly reduced pain
2).33 It is thought that the long-acting bupiva- intensity not just immediately (0-4 hours) postop-
eratively but also at 48 hours. These results were
caine reduces the afferent barrage of nocicep- not affected by whether lidocaine or placebo (sa-
tive input and prevents central sensitization to line) was administered preoperatively. The patients
pain; the benefit of long-acting local anesthetic in this study were under general anesthesia for the
is still significant at 48 hours even though the procedure.29,33 2-ANOVA = 2-way analysis of vari-
ance. Reprinted from Hersh EV, et al. The prescrip-
local anesthetic will have worn off.27-29 tion opioid abuse crisis and our role in it. Gen Dent.
Liposomal bupivacaine injectable suspen- 2018;66(4):10-13. Published with permission by the
sion (Exparel®, Pacira BioSciences) is a long- Academy of General Dentistry. © Copyright 2018
acting local anesthetic formulation that was by the Academy of General Dentistry. All rights
reserved.
granted Food and Drug Administration (FDA)
approval in 2011.34 This local anesthetic is indi-
cated for postsurgical analgesia by local (infil- with lipid bilayers arranged like a honeycomb,
tration) administration to the surgical site.34,35 with the bupivacaine in the aqueous core, that
It is not indicated as a replacement for preop- slowly releases the bupivacaine over time.34,35
erative local anesthesia.34,35 It is formulated Liposomal bupivacaine can persist for 96 hours
as a multivesicular liposomal formulation after administration, which makes it a valuable

8 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 1
NSAIDs are highly efficacious medications
for acute postoperative dental pain
because such pain is of
an inflammatory nature.
tool in keeping patients numb and comfortable
in the 2- to 3-day window of postoperative pain
and inflammation after removal of impacted
third molars.34,35 A thorough discussion of li-
posomal bupivacaine injectable suspension is
beyond the scope of this paper.
The use of liposomal bupivacaine may be cost
prohibitive at approximately $175 for a single-
use, single-patient vial of 133 mg/10 mL or $325
for a single-use, single-patient vial of 266 mg/20
mL.35 However, studies suggest that infiltration
with an appropriate volume of traditional bupi-
vacaine to cover the surgical site may be equally
effective in reducing pain scores.36 A prospective,
randomized, double-blinded trial comparing
pain scores, analgesic consumption, and soft-
tissue numbness in patients with untreated,
symptomatic, irreversible pulpitis with either
4 mL liposomal or 4 mL traditional bupivacaine
plus 1:200,000 epinephrine supports the use of
traditional bupivacaine for postoperative pain
control.36 The patients had no significant dif-
ferences in the amount of pain and analgesic
consumption for 3 days after the injections but
did report more soft-tissue numbness with the
liposomal formulation.36
Another prospective, randomized, double-
blind trial compared liposomal and regular
bupivacaine, also 4 mL each, on symptom-
atic, necrotic teeth after endodontic debride-
ment.37 The patients were followed for 5 days
postoperatively to assess pain, soft-tissue
anesthesia, the use of opioid escape medica-
tion, and the use of non-opioid analgesics.37
Success was defined as patients not using an
9 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
opioid and reporting no pain or mild pain.37
The success rate was statistically similar for
both groups, 29% for liposomal bupivacaine
and 22% for bupivacaine.37 It is notable that
there was no statistical difference in the
use of escape medication (opioids) in either
group.37 A study of patients after dental im-
paction surgery showed only modest benefits
for those treated with liposomal bupivacaine
over those receiving placebo postoperative-
ly.38 Further research is needed to explore the
utility of liposomal bupivacaine after trau-
matic dental procedures.
Future research exploring the risk-benefit
ratio of glucocorticoids and the selective cy-
clooxygenase-2 (COX-2) inhibitor celecoxib
also appears warranted. Glucocorticoids work
by inhibiting phospholipase A2, the enzyme
responsible for the release of arachidonic acid
from damaged cell membranes, therefore pre-
venting the synthesis of prostaglandins and
leukotrienes.39 Data support the reduction of
early and late edema as well as early trismus
after third-molar extraction when steroids are
injected submucosally.40
NSAIDs are highly efficacious medications for
acute postoperative dental pain because such
pain is of an inflammatory nature, but the side-
effect profile may preclude use in patients with
gastrointestinal ulcers, perforations, and bleeds,
or those with coagulopathies. NSAIDs interfere
with both COX-1 and COX-2 enzymes. COX-2
inhibitors, as their name implies, block COX-2
selectively and possess lower ulcerogenic and
bleeding effects than non-selective NSAIDs such
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 CONTINUING EDUCATION 1 PRESCRIPTION ANALGESIA

as ibuprofen and naproxen sodium.39 However, Ibuprofen demonstrated faster onset time
COX-2 inhibitors such as celecoxib have been and statistically superior analgesic efficacy
associated with an increased risk of heart attacks except at the time of redosing the second or
and strokes, at least when taken chronically. third dose (ie, hours 3, 4, and 8), which is
That factor prompted the drug manufacturer consistent with a shorter duration of action
Merck to remove rofecoxib (Vioxx®) from the compared with celecoxib.44 Patients in the
market. Subsequently the FDA also removed ibuprofen group were 50% less likely to take
the highly selective COX-2 inhibitor valdecoxib. a rescue analgesic than the celecoxib group in
Moreover, the FDA issued its most serious warn- the first 12 hours after impacted third-molar
ing, a black box warning, on all NSAIDs, includ- surgery.44 The recommended dosing for cele-
ing those available OTC and celecoxib.41,42 One coxib for acute pain is an initial dose of 400
double-blinded study evaluated the analgesic mg that can be followed by an additional 200
efficacy of diclofenac 50 mg, acetaminophen mg if needed on the first day. On subsequent
1,000 mg, celecoxib 400 mg, and placebo and days, the dosing is 200 mg every 12 hours as
found that all treatment groups were superior needed for pain.45 Given the side-effect profile
to placebo, and that celecoxib was as effective of COX-2 inhibitors and the delayed analgesic
as diclofenac for postoperative pain after minor onset of celecoxib in particular, the clinician
oral surgery procedures.43 The study lacked an should carefully review the patient’s medical
assessment of whether celecoxib resulted in less history for cardiovascular disease.42,45
postoperative bleeding.43
Another randomized, placebo-controlled, Data Demonstrate That NSAIDs
parallel-group study compared the efficacy Be the First-Line Medications for
of ibuprofen liquid-gels 400 mg and celecox- Acute Postoperative Dental Pain of
ib 200 mg.44 The results demonstrated that Moderate to Severe Intensity
both medications were superior to placebo. Analgesic studies have demonstrated the

wFIGURE 3

IBUPROFEN 400 mg + CODEINE 60 mg

IBUPROFEN 400 mg + CODEINE 60 mg (n=41)
(n=41)
PAIN INTENSITY DIFFERENCE SCORE

IBUPROFEN 400 mg (n=38)

1.0 2.0
PAIN RELIEF SCORE

IBUPROFEN 400 mg (n=38)

ASPIRIN 650 mg + CODEINE 60 mg
(n=45)

ASPIRIN 650 mg + CODEINE 60 mg

(n=45) ASPIRIN 650 mg (n=38)

0.5 1.0 CODEINE 60 mg (n=41)

ASPIRIN 650 mg (n=38)

PLACEBO (n=46)
CODEINE 60 mg (n=41)

PLACEBO (n=46)

0 1 2 3 4 0 1 2 3 4
HOUR HOUR

Fig 3. The graph on the left shows the mean pain intensity difference scores compared with time, whereas
the graph on the right shows the mean pain relief scores over time.47 Reprinted from Cooper SA, et al.
Analgesic efficacy of an ibuprofen-codeine combination. Pharmacotherapy. 1982;2(3):162-167. Published
with permission from John Wiley and Sons. Copyright © 1982 American College of Clinical Pharmacy.
Published by John Wiley & Sons, Inc. All rights reserved.

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 CONTINUING EDUCATION 1 PRESCRIPTION ANALGESIA

Fig 4. Mean pain relief scores over time for dental pain comparing ibuprofen, tramadol plus acetaminophen,
acetaminophen, tramadol, and placebo.49 Reprinted from Edwards JE, et al. Combination analgesic efficacy:
individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postopera-
tive pain. J Pain Symptom Manage. 2002;23(2):121-130. Published with permission from Elsevier. Copyright ©
2002 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

efficacy of NSAIDs in the management of has been demonstrated that acetaminophen,

moderate to severe postoperative dental
pain. They have included use of the Dental
Impaction Pain Model, one of the most wide-
ly used acute pain models.46 Much of these
data have been available since the early 1980s,
which only serves to heighten the tragedy of
the role of dental prescribing practices in the
opioid epidemic.3 Hundreds of trials involv-
ing thousands of patients illustrate the data
summarized in Figure 347 and justify the pre-
scribing regimens in Figure 1.27,28 Cooper et
al demonstrated that ibuprofen 400 mg has
superior analgesic efficacy to aspirin 650 mg
plus codeine 60 mg, followed by aspirin 650
mg, which was better than codeine 60 mg,
and lastly placebo (Figure 3).47 These data
originated from a 1982 trial in which aspirin
was used. However, acetaminophen can be
logically substituted for aspirin because it
although lacking anti-inflammatory activity,
is equianalgesic to aspirin: 650 mg of acet-
aminophen will produce equivalent analgesic
to 650 mg of aspirin.48
Edwards et al collected data from multiple
clinical trials involving dental pain and dem-
onstrated that the opioid tramadol was only
marginally better than the placebo control.49
Acetaminophen 650 mg demonstrated marked
improvement over tramadol 75 mg and placebo.
The combination of acetaminophen 650 mg
and tramadol 75 mg was slightly better than
acetaminophen 650 mg alone, demonstrat-
ing that the benefit of tramadol was secondary
to the pain relief from acetaminophen alone.
Lastly, ibuprofen 400 mg demonstrated supe-
rior analgesic efficacy and longer duration of
pain relief than the acetaminophen plus opioid
combination (Figure 4).49

11 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 1
Conclusions
There is an ongoing opioid crisis in the United
States, and prescription analgesics play a major
role in the exposure and potential for misuse,
abuse, and diversion of medications. In 2012,
dentists were the second-highest prescribers
of immediate-release opioids, after primary
care physicians.7,8 Dentists were also the top
prescribers for adolescents, and opioid use in
adolescence is associated with an increased risk
of future opioid misuse.9,13 Less than half the
opioids prescribed after surgical extractions
are typically used, leaving leftover medica-
tions for potential diversion, misuse, or abuse
by either the patient or other individuals with
access to the medications.5,19 Increased aware-
ness of the role of prescribing practices in the
opioid epidemic has resulted in changes in
guidelines and regulations, including state
and federal legislation, implementation of
PDMPs, and increased continuing education
requirements. The Dental Impaction Pain
Model, which has been widely used for nearly
4 decades, has shown that NSAIDs are effec-
tive, non-addicting analgesics for postsurgi-
cal dental pain.46 The multimodal analgesic
approach intercepts pain at various points
on the pain pathways and interferes with dif-
ferent processes by using medication in dif-
ferent drug classes. This approach produces
additive analgesia while reducing the dose of
any single analgesic, thus reducing the side
effects of each drug used. This concept is not
unusual in dentistry, with the ubiquitous use
of local anesthetic to prevent the transmis-
sion of afferent pain signals followed by the
prescription of some combination of NSAIDs,
acetaminophen, and opioids. The use of long-
acting local anesthesia can reduce the break-
through of pain, whereas NSAIDs should be
used as a first-line drug (or acetaminophen
when NSAIDs are contraindicated). Opioids
should be reserved for severe breakthrough
pain or when NSAIDs are contraindicated,
and the prescriptions should be minimized to
12 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
a 2- to 3-day course. Patients with persistent
pain should be evaluated before additional
opioids are prescribed.23,24,27,29
DISCLOSURE
Drs. Laniado, Badner, and Saraghi declared no conflicts of
interest. During the last 15 years, Dr. Hersh, representing the
Trustees of the University of Pennsylvania (Penn), has received
funding from Pfizer Consumer Healthcare, the maker of Advil®
products; AAI International, the original manufacturer of
diclofenac Prosorb (Zipsor®); and the National Institutes
of Health/National Institute on Drug Abuse for his role in
the development of and teaching part of the Penn multidisci-
plinary Pain Science course. The grant checks are written to the
University and not Dr. Hersh. He has also received consulting
compensation from Johnson & Johnson, the maker of Tylenol®
(acetaminophen) products and Motrin® IB (ibuprofen 200 mg);
and Bayer Pharmaceuticals, the maker of over-the-counter
naproxen sodium (Aleve®), for the expertise he provides review-
ing clinical research data.
ABOUT THE AUTHORS
Nadia Laniado, DDS, MPH
Assistant Professor, Department of Dentistry, Albert Einstein
College of Medicine, Bronx, New York; Assistant Professor,
Department of Epidemiology and Population Health, Albert
Einstein College of Medicine, Bronx, New York
Elliot V. Hersh, DMD, MS, PhD
Professor, Oral Surgery and Pharmacology, Director,
Division of Pharmacology, University of Pennsylvania School
of Dental Medicine, Philadelphia, Pennsylvania
Victor M. Badner, DMD, MPH
Chair, Department of Dentistry/OMFS, Jacobi Medical
Center and North Central Bronx Hospital, Bronx, New York
Mana Saraghi, DMD
Director, Dental Anesthesiology Residency Program, Jacobi
Medical Center, Bronx, New York; Assistant Professor,
Department of Dentistry, Albert Einstein College of Medicine,
Bronx, New York
Queries to the author regarding this course may be submitted
to authorqueries@aegiscomm.com.
REFERENCES
1. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. In-
creases in drug and opioid overdose deaths -- Unit-
ed States, 2000-2014. MMWR Morb Mortal Wkly
Rep. 2016;64(50-51)1378-1382.
2. Florence CS, Zhou C, Luo F, Xu L. The economic
burden of prescription opioid overdose, abuse, and
dependence in the United States, 2013. Med Care.
2016;54(10):901-906.
www.compendiumlive.com
 CONTINUING EDUCATION 1
3. Van Zee A. The promotion and marketing of Oxy-
Contin: commercial triumph, public health tragedy.
Am J Public Health. 2009;99(2):221-227.
4. Chisholm-Burns MA, Spivey CA, Sherwin E, et
al. The opioid crisis: origins, trends, policies, and
the roles of pharmacists. Am J Health Syst Pharm.
2019;76(7):424-435.
5. Maughan BC, Hersh EV, Shofer FS, et al. Unused
opioid analgesics and drug disposal following out-
patient dental surgery: a randomized controlled tri-
al. Drug Alcohol Depend. 2016;168:328-334.
6. Wardhan R, Chelly J. Recent advances in acute
pain management: understanding the mecha-
nisms of acute pain, the prescription of opioids,
and the role of multimodal pain therapy. F1000Res.
2017;6:2065.
7. Gupta N, Vujicic M, Blatz A. Opioid prescribing
practices from 2010 through 2015 among dentists in
the United States: what do claims data tell us? J Am
Dent Assoc. 2018;149(4):237-245.e6.
8. Lutfiyya MN, Gross AJ, Schvaneveldt N, et al. A
scoping review exploring the opioid prescribing
practices of US dental professionals. J Am Dent As-
soc. 2018;149(12):1011-1023.
9. Volkow ND, McLellan TA, Cotto JH, et al. Char-
acteristics of opioid prescriptions in 2009. JAMA.
2011;305(13):1299-1301.
10. Denisco RC, Kenna GA, O’Neil MG, et al. Preven-
tion of prescription opioid abuse: the role of the
dentist. J Am Dent Assoc. 2011;142(7):800-810.
11. Friedman JW. The prophylactic extraction of
third molars: a public health hazard. Am J Public
Health. 2007;97(9):1554-1559.
12. Compton WM, Jones CM, Baldwin GT, et al. Tar-
geting youth to prevent later substance use disor-
der: an underutilized response to the US opioid cri-
sis. Am J Public Health. 2019;109(S3):S185-S189.
13. Miech R, Johnston L, O’Malley PM, et al. Prescrip-
tion opioids in adolescence and future opioid mis-
use. Pediatrics. 2015;136(5):e1169-e1177.
14. Suda KJ, Durkin MJ, Calip GS, et al. Comparison
of opioid prescribing by dentists in the United States
and England. JAMA Netw Open. 2019;2(5):e194303.
15. Guy GP Jr, Zhang K, Bohm MK, et al. Vital
signs: changes in opioid prescribing in the United
States, 2006-2015. MMWR Morb Mortal Wkly Rep.
2017;66(26):697-704.
16. McCauley JL, Leite RS, Melvin CL, et al. Dental
opioid prescribing practices and risk mitigation
strategy implementation: identification of potential
targets for provider-level intervention. Subst Abus.
2016;37(1):9-14.
17. Hudgins JD, Porter JJ, Monuteaux MC, Bourgeois
FT. Trends in opioid prescribing for adolescents and
young adults in ambulatory care settings. Pediatrics.
2019;143(6).
18. Schroeder AR, Dehghan M, Newman TB, et al. As-
13 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
sociation of opioid prescriptions from dental clini-
cians for US adolescents and young adults with sub-
sequent opioid use and abuse. JAMA Intern Med.
2019;179(2):145-152.
19. Bicket MC, Long JJ, Pronovost PJ, et al. Prescription
opioid analgesics commonly unused after surgery: a
systematic review. JAMA Surg. 2017;152(11):1066-1071.
20. Fink DS, Schleimer JP, Sarvet A, et al. Association
between prescription drug monitoring programs
and nonfatal and fatal drug overdoses: a systematic
review. Ann Intern Med. 2018;168(11):783-790.
21. McCalmont JC, Jones KD, Bennett RM, Friend R.
Does familiarity with CDC guidelines, continuing ed-
ucation, and provider characteristics influence ad-
herence to chronic pain management practices and
opioid prescribing? J Opioid Manag. 2018;14(2):103-
116.
22. Keith DA, Shannon TA, Kulich R. The prescription
monitoring program data: what it can tell you. J Am
Dent Assoc. 2018;149(4):266-272.
23. Rasubala L, Pernapati L, Velasquez X, et al. Im-
pact of a mandatory prescription drug monitoring
program on prescription of opioid analgesics by
dentists. PloS One. 2015;10(8):e0135957.
24. American Dental Association announces new
policy to combat opioid epidemic [news release].
American Dental Association. https://www.ada.
org/en/press-room/news-releases/2018-archives/
march/american-dental-association-announces-
new-policy-to-combat-opioid-epidemic. Published
March 26, 2018. Accessed June 24, 2019.
25. Hollingshead NA, Meints S, Middleton SK, et al.
Examining influential factors in providers’ chronic
pain treatment decisions: a comparison of physi-
cians and medical students. BMC Med Educ. 2015;
15:164.
26. Contreras OA, Stewart D, Valachovic RW. The
Role of Dental Education in the Prevention of Opioid
Prescription Drug Misuse. Washington, DC: Ameri-
can Dental Education Association; March 2018.
27. Moore PA, Hersh EV. Combining ibuprofen and ac-
etaminophen for acute pain management after third-
molar extractions. J Am Dent Assoc. 2013;144(8):898-
908.
28. Hersh EV, Kane WT, O’Neil MG. Prescribing rec-
ommendation for the treatment of acute pain in den-
tistry. Compend Contin Educ Dent. 2011;32(3):22-30.
29. Hersh EV, Saraghi M, Moore PA. The prescrip-
tion opioid abuse crisis and our role in it. Gen Dent.
2018;66(4):10-13.
30. Krenzelok EP, Royal MA. Confusion: acetamin-
ophen dosing changes based on NO evidence in
adults. Drugs R D. 2012;12(2):45-48.
31. Dionne RA. Suppression of dental pain by the
preoperative administration of flurbiprofen. Am J
Med. 1986;80(3A):41-49.
32. Dionne RA, Cooper SA. Evaluation of preopera-
www.compendiumlive.com
 CONTINUING EDUCATION 1
tive ibuprofen for postoperative pain after removal
of third molars. Oral Surg Oral Med Oral Pathol.
1978;45(6):851-856.
33. Gordon SM, Brahim JS, Dubner R, et al. Attenu-
ation of pain in a randomized trial by suppression of
peripheral nociceptive activity in the immediate post-
operative period. Anesth Analg. 2002;95(5):1351-1357.
34. Saraghi M, Hersh EV. Three newly approved an-
algesics: an update. Anesth Prog. 2013;60(4):178-187.
35. Exparel prescribing information. San Diego,
CA: Pacira Pharmaceuticals, Inc.; 2018.
36. Bultema K, Fowler S, Drum M, et al. Pain reduc-
tion in untreated symptomatic irreversible pulpitis
using liposomal bupivacaine (Exparel): a prospec-
tive, randomized, double-blind trial. J Endod. 2016;
42(12):1707-1712.
37. Glenn B, Drum M, Reader A, et al. Does liposomal
bupivacaine (Exparel) significantly reduce postop-
erative pain/numbness in symptomatic teeth with
a diagnosis of necrosis? A prospective, randomized,
double-blind trial. Endod. 2016;42(9):1301-1306.
38. Lieblich SE, Hassan D. Liposomal bupivacaine
use in third molar impaction surgery: INNOVATE
study. Anesth Prog. 2017;64(3):127-135.
39. Butterworth JF, Mackey DC, Wasnick JD. Clini-
cal Anesthesiology. 5th ed. New York, NY: McGraw-
Hill Companies; 2013.
40. Chen Q, Chen J, Hu B, et al. Submucosal injec-
tion of dexamethasone reduces postoperative dis-
comfort after third-molar extraction: a systematic
review and meta-analysis. J Am Dent Assoc. 2017;
148(2):81-91.
41. Lenzer J. FDA advisers warn: COX 2 inhibitors
increase risk of heart attack and stroke. BMJ. 2005;
14 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
PRESCRIPTION ANALGESIA
330(7489):440.
42. FDA Drug Safety Communication: FDA strength-
ens warning that non-aspirin nonsteroidal anti-in-
flammatory drugs (NSAIDs) can cause heart attacks
or strokes. Food and Drug Administration. https://
www.fda.gov/drugs/drug-safety-and-availability/
fda-drug-safety-communication-fda-strengthens-
warning-non-aspirin-nonsteroidal-anti-inflammatory.
Published July 9, 2015. Updated February 26, 2018.
Accessed November 20, 2019.
43. Hanzawa A, Handa T, Kohkita Y, et al. A compara-
tive study of oral analgesics for postoperative pain af-
ter minor oral surgery. Anesth Prog. 2018;65(1):24-29.
44. Doyle G, Jayawardena S, Ashraf E, et al. Effi-
cacy and tolerability of nonprescription ibuprofen
versus celecoxib for dental pain. J Clin Pharmacol.
2002;42(8):912-919.
45. Celebrex prescribing information. New York,
NY: Pfizer, Inc.; 2016.
46. Cooper SA, Desjardins PJ. The value of the
dental impaction pain model in drug development.
Methods Mol Biol. 2010;617:175-190.
47. Cooper SA, Engel J, Ladov M, et al. Analge-
sic efficacy of an ibuprofen-codeine combination.
Pharmacotherapy. 1982;2(3):162-167.
48. Cooper SA. Comparative analgesic efficacies
of aspirin and acetaminophen. Arch Intern Med.
1981;141(3 Spec No):282-285.
49. Edwards JE, McQuay HJ, Moore RA. Combi-
nation analgesic efficacy: individual patient data
meta-analysis of single-dose oral tramadol plus
acetaminophen in acute postoperative pain. J Pain
Symptom Manage. 2002;23(2):121-130.
www.compendiumlive.com
 CONTINUING EDUCATION 1 QUIZ 2 Hours CE Credit

Prescribing Analgesics for Postoperative Dental Pain

Nadia Laniado, DDS, MPH; Elliot V. Hersh, DMD, MS, PhD;
Victor M. Badner, DMD, MPH; and Mana Saraghi, DMD

TAKE THIS FREE CE QUIZ BY CLICKING HERE: COMPENDIUMLIVE.COM/GO/DENTALPAIN1

ENTER PROMO CODE: INNDP1

1. In 2014, what percent of drug overdose 6. What term means to intercept pain at
deaths were attributable solely to opioids? multiple areas along the peripheral and
A. 44% central pain pathways?
B. 61%  A. first line therapy
C. 73% B. PDMP
D. unknown C. multimodal analgesia
D. all of the above
2. The beginning of the opioid epidemic can be
traced to: 7. The maximum daily dose for ibuprofen
A. the rise of multimodal analgesia. should not exceed:
B. a black box warning on all NSAIDs. A. 2,400 mg.
C. a sustained-release formulation of B. 3,000 mg.
oxycodone. C. 3,600 mg.
D. overestimating the magnitude of patients’ D. 4,000 mg.
postoperative pain.
8. Administering medication before an incision
3. Dentists are the top prescriber of opioids for: will limit the production of:
A. emergencies. A. prostaglandins.
B. adolescents. B. a
 rachidonic acid.
C. postoperative pain. C. blood platelets.
D. none of the above D. liposomal bupivacaine.

4. What oral medications are equivalent to oral 9. Given the side-effect profile of COX-2
morphine 10 mg (10 MME)? inhibitors, the clinician should carefully
A. oxycodone 5 mg review the patient’s medical history for:
B. hydrocodone 10 mg A. cardiovascular disease.
C. codeine 60 mg B. rheumatoid arthritis.
D. all of the above C. gastrointestinal ulcers.
D. acetaminophen use.
5. What percent of opioid prescriptions are for
nonsurgical dental visits? 10. It has been demonstrated that
A. one-quarter acetaminophen, although lacking anti-
B. one-third inflammatory activity, is equianalgesic to:
C. one-half A. liposomal bupivacaine.
D. two-thirds B. opioids.
C. glucocorticoids.
D. aspirin.

Course is valid from 4/1/2020 to 4/30/2023. Participants

must attain a score of 70% on each quiz to receive credit. Par-
ticipants receiving a failing grade on any exam will be notified
and permitted to take one re-examination. Participants will
receive an annual report documenting their accumulated
credits, and are urged to contact their own state registry
boards for special CE requirements.
AEGIS Publications, LLC, is an ADA CERP Recognized
Provider. ADA CERP is a service of the American Dental Approval does not imply acceptance
by a state or provisional board of
Association to assist dental professionals in identifying quality
providers of continuing dental education. ADA CERP does not dentistry or AGD endorsement. The
approve or endorse individual courses or instructors, nor does current term of approval extends from
it imply acceptance of credit hours by boards of dentistry. 1/1/2017 to 12/31/2022.
Concerns or complaints about a CE provider may be directed Provider #: 209722.
to the provider or to ADA CERP at www.ada.org/cerp.

15 COMPENDIUM EBOOK SERIES April 2020 || Volume

Volume 41
x Number
Numberx8 www.compendiumlive.com
 CONTINUING EDUCATION 2 INTRANASAL KETOROLAC

Characterization and
Treatment of Postsurgical
Dental Implant Pain Employing
Intranasal Ketorolac
Rebecca Bockow, DDS, MS; Jonathan Korostoff, DMD, PhD; Andres Pinto, DMD, MPH; Matthew Hutcheson, MS; Stacey A.
Secreto, CRC; Laura Bodner, DMD; and Elliot V. Hersh, DMD, MS, PhD

ABSTRACT: The intensity and duration of pain following surgical placement of dental im-
plants has not been well studied. Thus, the aim of this open-label study was to characterize
the nature of postsurgical pain following the placement of one to three implants. The sec-
ondary goal was to explore the analgesic efficacy and tolerability of intranasal ketorolac in
this patient population. Following implant surgery, postoperative pain was rated moderate
or severe in 25/28 patients (89%), requiring prn analgesic dosing for up to 3 days in 14/25
individuals (56%). Intranasal ketorolac displayed an analgesic onset within 20 minutes, a
duration of at least 6 hours, and was well tolerated by the cohort with brief stinging of the
nasal mucosa reported by 9/25 individuals (36%).

LEARNING OBJECTIVES

•Discuss the nature of
postsurgical pain in patients
undergoing dental implant
surgery with respect to the
need for postoperative pain
medication
•Describe the efficacy and
tolerability of intranasal
ketorolac for treatment of
moderate to moderately
severe pain
•List common side effects
of intranasal ketorolac as
reported by patients

T
he use of dental implants has
quickly become a primary meth-
od for replacing missing teeth
due to their high level of predict-
ability and patient acceptance.1-4
By 2006, dentists in the United States had
placed 5.5 million dental implants, and this
number continues to grow.5 As of 2007, more
than 30 million Americans were reported
to have missing teeth in one or both jaws.6
With the aging population increasingly seek-
ing dental implants to replace missing teeth,
a growing number of general dentists and
dental specialists are being trained to place
and restore them.
Despite the ever-increasing demand for
implant-supported restorations, the pain
patients experience and the effectiveness of
analgesic interventions following the surgi-
cal component of treatment has not been well
studied. Hundreds of papers have been pub-
lished on the pain and effectiveness of anal-
gesic interventions following the removal of
impacted third molars. In contrast, a PubMed
search between the years 1970 and 2012 us-
ing the MeSH terms dental implant pain or

16 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 2
“Intranasal ketorolac has demonstrated efficacy in
patients experiencing abdominal, orthopedic, and
impacted third molar surgery pain.”
postsurgical dental implant pain revealed
six papers in the literature evaluating the in-
tensity or duration of implant surgery pain
or the effectiveness of analgesic therapy.7-12
The overwhelming majority of participants
enrolled in impacted third molar pain stud-
ies are young healthy adults, whereas implant
patients tend to be significantly older, with
a variety of concomitant medical conditions
requiring the intake of multiple medications
to treat these comorbid conditions.
Ketorolac is a non-steroidal anti-inflam-
matory drug (NSAID) with FDA approval
for the short-term (5 days or less) treatment
of moderate to moderately severe pain. It is
available as an oral, parenteral, and most re-
cently (May 17, 2010) an intranasal formu-
lation. This newest formulation (SPRIX®,
Luitpold Pharmaceuticals, Inc., www.luit-
pold.com) comes in a disposable, multi-dose,
metered spray device that allows patients to
self-administer the drug outside of the hospi-
tal setting.13-16 The recommended dose is 31.5
mg (one 15.75 mg spray in each nostril) every
6 to 8 hours for patients under the age of 65
years, with half this dose (one 15.75 mg spray
in only one nostril) recommended for those
65 years or older.16 Intranasal ketorolac has
demonstrated efficacy in patients experienc-
ing abdominal, orthopedic, and impacted third
molar surgery pain.13,17-19 Its absorption from
the nasal mucosa is as rapid as the intramus-
cular administration of the drug.20
The purpose of this open-labeled multi-dose
pilot study was to characterize the nature of
postsurgical pain in patients undergoing rou-
tine dental implant surgery with respect to the
17 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
INTRANASAL KETOROLAC
percentage of participants requiring postop-
erative pain medication and their duration of
analgesic dosing. The authors also explored
the efficacy and tolerability of intranasal ke-
torolac in these patients.
Methods
The University of Pennsylvania Institutional
Review Board (IRB) approved the protocol
and informed consent form, and the trial was
listed in ClinicalTrials.gov under the identifier
NCT01490931. Patients between the ages of
18 to 64 years of age who were scheduled for
the placement of one to three dental implants
without the need for significant bone grafting
were invited to participate in this open-label
study. Key exclusion criteria included NSAID
intolerance or allergy, the use of bupivacaine as
a local anesthetic, the need for sedative drugs
other than nitrous oxide, pregnancy, and the
use of any antiplatelet or anticoagulant agent
other than low-dose (81 mg to 325 mg) aspirin.
Dental implant surgery was carried out ac-
cording to standard of care. Patients self-ad-
ministered the ketorolac nasal spray (15.75
mg in each nostril) according to the package
insert guidelines and under the supervision of
the research coordinator or one of the inves-
tigators (RB) once they began to experience
at least moderate pain indicated by scores of ≥
40 mm on a 100 mm visual analog scale (VAS,
0 = no pain, 100 = worst possible pain) and
a score of ≥ 2 on a 0 to 3 ordinal scale (none,
mild, moderate, or severe pain). Pain intensity
on the VAS and the ordinal scale and pain re-
lief on a 0 to 4 ordinal scale (no relief, a little
relief, some relief, a lot of relief, complete
www.compendiumlive.com
 CONTINUING EDUCATION 2 INTRANASAL KETOROLAC

relief ) were assessed for 6 hours, as was the
onset of first perceptible and meaningful relief
employing a double stopwatch technique.21
Acetaminophen 650 mg was available as a
rescue analgesic if sufficient pain relief was
not obtained or pain relief dissipated before 6
hours. At the 6-hour time point or at the time
of requesting rescue analgesic, patients gave
their overall impression of the intranasal ke-
torolac from poor to excellent.21
contraindication for the administration of all
NSAIDs), another had a body mass index (BMI)
of 31 which at the time precluded enrollment
(maximum BMI was 29 until an IRB-approved
amendment increased it to 33), and a third did
not receive his implants because of the need for
significant bone grafting during surgery. Three
TABLE 1

Patients then transitioned into a multi-dose Demographic and Baseline Pain

take-home phase of the study where they were Characteristics of Study Participants
allowed to administer the ketorolac nasal Who Took at Least One Dose of
spray every 6 hours on a prn basis when and Intranasal Ketorolac
if they felt the need to medicate for pain con- GENDER, n (%)
trol. They completed a take-home diary where Male: 11 (44%)
the time of dosing, the pain intensity at dosing, Female: 14 (56%)
the time of any rescue acetaminophen they in-
gested, and any adverse events they may have AGE, YEARS
experienced were recorded. Mean (SD): 48.6 (10.4)
Range (min-max): 22.8-64.0
Statistical Analysis
Time-effect curves for changes in pain intensity RACE, n (%)
and pain relief, as well as the cumulative per- Black: 5 (20%)
centage of participants re-medicating with ac- White: 18 (72%)
etaminophen at each time point through the ini- Asian: 1 (4%)
tial 6-hour post-dosing period were constructed. Other: 1 (4%)
The percentage of patients who rated intranasal
ketorolac as poor, fair, good, very good, or excel- WEIGHT, LBS
lent was also calculated. Changes in pain inten- Mean (SD): 164.8 (34.3)
sity on both the VAS and the 0 to 3 ordinal scale Range (min-max): 122-225
were statistically compared to baseline pain uti-
lizing paired t-tests with Bonferroni corrections DURATION OF SURGERY (HOURS)
for multiple comparisons. The median onsets Mean (SD): 1.6 (0.8)
of first perceptible and meaningful relief (with Range (min-max): 0.75-3.67
95% confidence intervals) were calculated and
then used to construct Kaplan-Meier curves of TIME TO MEDICATION FROM END OF
the distribution of pain relief times. SURGERY (HOURS)
Mean (SD): 1.4 (0.9)
Results Range (min-max): 0.33-3.25
A total of 31 patients consented to the study
and 25 were dosed with intranasal ketorolac BASELINE PAIN, VAS mm
31.5 mg. Of the six patients who were not dosed, Mean (SD): 54.4 (14.3)
one reported a history of aspirin-sensitive asth- Range: 40-90
ma immediately before surgery (an absolute

18 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 2 INTRANASAL KETOROLAC

100 4
90
80
Pain Intensity Score (mm)

3
70
* p 0.0001 vs. baseline pain

Pain Relief Score

60
50 2
40
30
* * 1
20 *
* * * * * *
10
0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Fig 1. Time (hours) Fig 2 Time (hours)

Fig 1. Mean ± standard error of the time-effect curve for VAS pain intensity from immediately prior to dos-
ing (zero hours) through 6 hours. Asterisks indicate a significant reduction in pain intensity compared to
baseline (p ≤ 0.0001). Fig 2. Mean ± standard error of the time-effect curve for pain relief from immediately
prior to dosing (zero hours) through 6 hours.

patients who received their implants did not 20 minutes), high peak effects between 40
achieve the required VAS pain intensity score minutes and 4 hours, and an apparent dura-
of 40 mm within 4 hours of the completion of tion of action at least through 6 hours. The me-
their surgery. Therefore, 89% (25/28) of the par- dian onsets of first perceptible and meaningful
ticipants obtained a level of at least moderate pain relief were 86 seconds (95% confidence
postsurgical pain within 4 hours after the place- interval; 64 to 172 sec) and 172 seconds (95%
ment of one to three implants. The demographic confidence interval; 132 to 735 sec), respec-
characteristics and the mean baseline pain score tively, again confirming the rapid onset of the
of the study population are shown in Table 1. drug. The Kaplan-Meier curve of the times to
As displayed in Figure 1, mean VAS pain
intensity scores rapidly decreased following
self-administration of intranasal ketorolac TABLE 2

31.5 mg. By the 20-minute time point, the

Number of Participants Dosing with Pain
mean VAS score had decreased from 54.4 mm
Medication and the Mean Numbers of Doses
to 14.8 mm. Mean peak reduction in pain in-
Taken by Those Individuals Who Took at
tensity appeared to occur within 40 minutes,
Least One Dose of Intranasal Ketorolac
with the analgesic effect still being prominent
at 6 hours (a mean VAS of 19.5 mm). All mean
VAS pain intensity scores from 20 minutes DAY NO. OF SUBJECTS (%) NO. OF DOSES * (SD)
through 6 hours were significantly lower (p <
0.0001) than the mean baseline pain intensity 1 25 (100%) 1.8 (0.4) range: 1-2
score prior to dosing. The reduction in pain 2 18 (72%) 1.8 (0.9) range: 1-4
intensity on the 0 to 3 ordinal scale mirrored 3 14 (56%) 1.7 (0.9) range: 1-4
the VAS data with respect to time course and 4 10 (40%) 1.9 (1.1) range: 1-4
magnitude of effect. 5 6 (24%) 2.0 (1.3) range: 1-4
The time effect curve for mean pain relief
(Figure 2) also displayed a rapid onset (within * includes any rescue dosing taken

19 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 2 INTRANASAL KETOROLAC

100%
impressions (Figure 5) of intranasal ketoro-
lac were extremely favorable, with 92% of pa-
80%
tients rating the drug as very good or excellent.
Twenty of the 25 patients (80%) who complet-
ed the initial 6-hour evaluation period required
60% additional doses of intranasal ketorolac and/or
rescue medication at home. Table 2 shows the
Proportion

percentage of patients still administering pain

40% medication and the mean number of doses they
were taking per day during the 5-day evaluation
period. On days two through four, one or two
20%
patients ingested supplemental acetaminophen
in addition to intranasal ketorolac, while one
patient discontinued intranasal ketorolac for in-
0%
0 5 10 1 5 20 2 5 30 3 5 40 4 5 50 5 5 60 6 5 adequate pain control and required a prescrip-
Fig 3 Time (minutes) tion containing an opioid analgesic through day
five. The most common side effect reported by
100% patients during the initial dosing and take-home
90% dosing periods was transient nasal burning (36%
80%
or 9/25) on drug administration. Table 3 lists
Cumulative % Using Rescue

70%
the side effects reported by study patients. No
60%
50%
patient discontinued taking intranasal ketorolac
40%
because of an adverse event.
30%
20% Discussion
10% It has previously been reported that the pain pa-
0% tients experience after routine dental implant
0 1 2 3 4 5 6 surgery is generally mild in nature.7,10-12 In the
Fig 4 Time (hours)
current study, 25 of 28 subjects receiving one to
Fig 3. Kaplan-Meier curve of onset times to meaning-
three implants without significant bone grafting
ful relief. experienced pain of at least a moderate intensity
within 4 hours after the completion of surgery.
Fig 4. Cumulative percentage of participants taking It has been reported that the experience of the
rescue medication at or before each specific time
point. operator (periodontist or oral surgeon versus
periodontal resident) appears to correlate with
the degree of dental implant postoperative pain
meaningful relief among participants is shown following implant surgery.12 In the current study,
in Figure 3. Only one participant did not ob- the three subjects who did not require analgesic
tain meaningful pain relief. medication within the 4 hours immediately fol-
Figure 4 illustrates the cumulative percent- lowing their surgery had their implants placed
age of participants requiring rescue analge- by residents. Of the 25 participants who dosed
sic (aceta-minophen 650 mg) within 6 hours. with intranasal ketorolac, residents performed
Only 8% (2/25) of patients ingested rescue 18 of the surgeries, and an experienced periodon-
analgesic by 4 hours post-dosing, with 28% tist or oral surgeon performed seven. However,
(7/25) patients doing so by 6 hours. Overall the authors cannot rule out that average pain

20 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8 www.compendiumlive.com

 CONTINUING EDUCATION 2
“In the participants in this study, intranasal ketorolac
displayed a rapid analgesic onset, high peak effects,
and an acceptable duration of action.”
scores could have been less if only experienced
clinicians performed the surgeries. More than
50% of this study’s cohort required analgesic
medication for at least 3 days following what is
considered routine dental implant surgery. It is
likely that subjects with more traumatic surgery
would experience greater levels of pain and dose
more frequently for a longer period of time.10
In the participants in this study, intranasal
ketorolac displayed a rapid analgesic onset,
high peak effects, and an acceptable duration
of action. A rapid onset of analgesic activity
is desirable because it enhances patient com-
fort and reduces the chance of excessive drug
dosing. If additional analgesics are needed
for breakthrough pain within the 6-hour
dosing interval, acetaminophen or an acet-
aminophen/opioid combination drug can be
safely given in conjunction with NSAIDs like
ketorolac.17-19,22,23 According to the package
insert, other NSAIDs including preparations
containing ibuprofen or aspirin should not be
administered concurrently with any formula-
tion of ketorolac because of the risk of addi-
tive gastrointestinal bleeding and/or toxicity.16
The most common adverse event experienced
by participants in this study was a burning or
stinging feeling of the nasal mucosa immedi-
ately after dosing, which dissipated rapidly.
This common side effect was reported by par-
ticipants in other studies and is listed in the
package insert of the drug.16,17,19,24
Non-steroidal anti-inflammatory drugs,
such as intranasal ketorolac, should represent
the first line drugs for most types of postsurgi-
cal dental pain because of their proven efficacy
and favorable side-effect profile.25 Unlike the
21 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
INTRANASAL KETOROLAC
oral formulation of ketorolac, which accord-
ing to package insert guidelines should only
be prescribed for patients who were origi-
nally taking parenteral ketorolac for pain,26
the intranasal formulation can be used as the
initial pain treatment. Because of ketorolac’s
high ulcerogenic potential, intranasal ketoro-
lac should still not be used for more than 5
days.16 Additional black box warnings on the
package insert of intranasal ketorolac include
contraindications in patients with poor kidney
function and those with a high bleeding risk.16
While opioid-containing analgesics remain
the most popular drugs in treating acute post-
surgical pain,27they produce a high incidence
of drowsiness, dizziness, nausea, and constipa-
tion compared to NSAID analgesics.25,28 Only
one patient (4%) in this study reported an
opioid-like side effect (constipation).
The major weakness of this study was its
open-label design, and it lacked a placebo con-
trol and an active comparator drug. The study
was also not powered to determine differences
between the sites of implant placement and
the number of implants placed.
Conclusion
The newest formulation of ketorolac, an intra-
nasal formulation, is available in a disposable,
multi-dose, metered spray device that allows
patients to self-administer the drug outside
of the hospital setting. Whether intranasal
ketorolac offers advantages in onset or peak
effects over other FDA-approved oral and less
costly NSAIDs in treating postsurgical dental
implant pain can only be verified with well-
designed clinical trials.
www.compendiumlive.com
 CONTINUING EDUCATION 2
DISCLOSURE
This study was supported by a grant from Luitpold Pharmaceuticals, Inc.,
Shirley, New York. Dr. Hersh was a recipient of the grant from Luitpold
Pharmaceuticals that funded this study, and he and Dr. Bockow each received
travel grants from Luitpold Pharmaceuticals to present some of this data at
the Academy of Osseointegration 2013 Annual Meeting. Mr. Hutcheson was
a paid consultant for this study.
ABOUT THE AUTHORS
Rebecca Bockow, DDS, MS
Resident in orthodontics and periodontics, Departments of
Orthodontics and Periodontics, School of Dental Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania
Jonathan Korostoff, DMD, PhD
Associate Professor of Periodontics, Director of the
Master of Science in Oral Biology Program, Department
of Periodontics, School of Dental Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania
Andres Pinto, DMD, MPH
Associate Professor of Oral Medicine and Community
Oral Health, Director of Oral Medicine Services and
Chief, Division of Community Oral Health, Department of
Oral Medicine, School of Dental Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania
Matthew Hutcheson, MS
Adjunct Professor, Departments of Education, Widener
University, Chester, Pennsylvania, and Delaware Valley
College, Doylestown, Pennsylvania; Partner, Tegra Analytics,
Doylestown, Pennsylvania
Stacey A. Secreto, CRC
Clinical Research Coordinator, Department of Oral Surgery
and Pharmacology, School of Dental Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania
Laura Bodner, DMD
Resident, Department of Orthodontics, School of Dental
Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania
Elliot V. Hersh, DMD, MS, PhD
Director, Division of Pharmacology and Therapeutics,
Professor, Oral and Maxillofacial Surgery and
Pharmacology, School of Dental Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania
Queries to the author regarding this course may be submitted
to authorqueries@aegiscomm.com.
REFERENCES
1. Zarb GA. Introduction to osseointegration in clinical
dentistry. J Prosthet Dent. 1983;49(6):824.
22 COMPENDIUM EBOOK SERIES April 2020 | Volume 41 Number 8
INTRANASAL KETOROLAC
2. Schmitt A, Zarb GA. The longitudinal clinical effec-
tiveness of osseointegrated dental implants for single-
tooth replacement. Int J Prosthodont. 1993;6(2):197-
202.
3. Zarb GA, Schmitt A. The longitudinal clinical effec-
tiveness of osseointegrated dental implants in poste-
rior partially edentulous patients. Int J Prosthodont.
1993;6(2):189-196.
4. Zarb GA, Schmitt A. The longitudinal clinical effec-
tiveness of osseointegrated dental implants in ante-
rior partially edentulous patients. Int J Prosthodont.
1993;6(2):180-188.
5. American Academy of Implant Dentistry website.
http://www.aaid-implant.org/about/Press_Room/
Dental_Implants_FAQ.html. Accessed Aug 11, 2012.
6. American Dental Association website. 2007 Sur-
vey on Surgical Dental Implants, Amalgam Resto-
rations, and Sedation. http://www.ada.org/1443.
aspx. Accessed August 10, 2012.
7. Al-Khabbaz AK, Griffin TJ, Al-Shammari KF. Assess-
ment of pain associated with surgical placement of
dental implants. J Periodontol. 2007;78(2):239-246.
8. Karabuda ZC, Bolukbasi N, Aral A, et al. Compari-
son of analgesic and anti-inflammatory efficacy of
selective and non-selective cyclooxygenase-2 in-
hibitors in dental implant surgery. J Periodontol.
2007;78(12):2284-2288.
9. Biron RT, Hersh EV, Barber HD, Seckinger RJ. A pilot
investigation: post-surgical analgesic consumption by
dental implant patients. Dentistry. 1996;16(3):12-13.
10. Bölükbasi N, Ersanli S, Basegmez C, et al. Efficacy
of quick-release lornoxicam versus placebo for acute
pain management after dental implant surgery: a ran-
domised placebo-controlled triple-blind trial. Eur J
Oral Implantol. 2012;5(2):165-173.
11. González-Santana H, Peñarrocha-Diago M, Gua-
rinos-Carbó J, Balaguer-Martínez J. Pain and inflam-
mation in 41 patients following the placement of
131 dental implants. Med Oral Patol Oral Cir Bucal.
2005;10(3):258-263.
12. Hashem AA, Claffey NM, O’Connell B. Pain
and anxiety following the placement of den-
tal implants. Int J Oral Maxillofac Implants.
2006;21(6):943-950.
13. Grant GM, Mehlisch DR. Intranasal ketorolac for
pain secondary to third molar impaction surgery: a
randomized, double-blind, placebo-controlled trial. J
Oral Maxillofac Surg. 2010;68(5):1025-1031.
14. Bacon R, Newman S, Rankin L, et al. Pulmonary
and nasal deposition of ketorolac tromethamine solu-
tion (SPRIX) following intranasal administration. Int J
Pharm. 2012;431(1-2):39-44.
15. Boyer KC, McDonald P, Zoetis T. A novel formula-
tion of ketorolac tromethamine for intranasal admin-
istration: preclinical safety evaluation. Int J Toxicol.
2010;29(5):467-478.
16. SPRIX (ketorolac tromethamine) Nasal Spray
www.compendiumlive.com
 CONTINUING EDUCATION 2
[package insert]. Shirley, NY: Regency Therapeutics;
2011.
17. Singla N, Singla S, Minkowitz HS, et al. Intranasal
ketorolac for acute postoperative pain. Curr Med Res
Opin. 2010;26(8):1915-1923.
18. Moodie JE, Brown CR, Bisley EJ, et al. The safe-
ty and analgesic efficacy of intranasal ketorolac
in patients with postoperative pain. Anesth Analg.
2008;107(6):2025-2031.
19. Brown C, Moodie J, Bisley E, Bynum L. Intranasal
ketorolac for postoperative pain: a phase 3, double-
blind, randomized study. Pain Med. 2009;10(6):1106-
1114.
20. McAleer SD, Majid O, Venables E, et al. Pharma-
cokinetics and safety of ketorolac following single in-
tranasal and intramuscular administration in healthy
volunteers. J Clin Pharmacol. 2007;47(1)13-18.
21. Hersh EV, Levin LM, Cooper SA, et al. Ibuprofen liqui-
gel in oral surgery pain. Clin Ther. 2000;22(11):1306-
1318.
22. Breivik EK, Barkvoll P, Skovlund E. Combining diclof-
enac with acetaminophen or acetaminophen-codeine
after oral surgery: a randomized, double-blind single-
dose study. Clin Pharmacol Ther. 1999;66(6):625-635.
23. Mehlisch DR, Aspley S, Daniels SE, Bandy DP. Com-
parison of the analgesic efficacy of concurrent ibupro-
fen and paracetamol with ibuprofen or paracetamol
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INTRANASAL KETOROLAC
alone in the management of moderate to severe acute
postoperative dental pain in adolescents and adults: a
randomized, double-blind, placebo-controlled, paral-
lel-group, single-dose, two-center, modified factorial
study. Clin Ther. 2010;32(5):882-895.
24. Turner CL, Eggleston GW, Lunos S, et al. Sniffing
out endodontic pain: use of an intranasal analgesic in
a randomized clinical trial. J Endod. 2011;37(4):439-
444.
25. Hersh EV, Kane WT, O’Neil MG, et al. Prescribing
recommendations for the treatment of acute pain in
dentistry. Compend Contin Educ Dent. 2011;32(3):22-
30.
26. TORADOL (ketorolac tromethamine) tablet, film
coated [package insert]. San Francisco, CA: Ge-
nentech Inc. http://dailymed.nlm.nih.gov/dailymed/
lookup.cfm?setid=c0336606-7366-41ce-9cef-
aa6524b92b11. Accessed August 24, 2012.
27. Hersh EV, Pinto A, Moore PA. Adverse drug inter-
actions involving common prescription and over-the-
counter analgesic agents. Clin Ther. 2007;29(sup-
pl):2477-2497.
28. Cooper SA, Precheur H, Rauch D, et al. Evalua-
tion of oxycodone and acetaminophen in treatment
of postoperative dental pain. Oral Surg Oral Med Oral
Pathol. 1980;50(6):496-501.
www.compendiumlive.com
 CONTINUING EDUCATION 1 QUIZ
Characterization and Treatment of Postsurgical Dental
Implant Pain Employing Intranasal Ketorolac
Rebecca Bockow, DDS, MS; Jonathan Korostoff, DMD, PhD; Andres Pinto, DMD, MPH; Matthew
Hutcheson, MS; Stacey A. Secreto, CRC; Laura Bodner, DMD; and Elliot V. Hersh, DMD, MS, PhD
TAKE THIS FREE CE QUIZ BY CLICKING HERE: COMPENDIUMLIVE.COM/GO/DENTALPAIN2
ENTER PROMO CODE: INNDP2
1. A PubMed search between 1970 and 2012
using the MeSH terms dental implant pain or
postsurgical dental implant pain revealed
how many papers in the literature evaluating
the intensity or duration of implant surgery
pain or the effectiveness of analgesic
therapy?
A. six B. 67
C. 117 D. hundreds
2. The overwhelming majority of participants
enrolled in impacted third molar pain studies
are:
A. male.
B. female.
C. young healthy adults.
D. older patients with concomitant medical
conditions.
3. Intranasal ketorolac has demonstrated
efficacy in patients experiencing what type of
pain?
A. abdominal
B. orthopedic
C. impacted third molar surgery
D. all of the above
4. In the current study, how many of 28
subjects receiving one to three implants
without significant bone grafting experienced
pain of at least a moderate intensity within 4
hours after the completion of surgery?
A. 5
B. 15
C. 20
D. 25
5. What percentage of this study’s cohort
required analgesic medication for at least 3
days following routine dental implant
surgery?
A. 9% B. 18%
C. 36% D. more than 50%
Course is valid from 4/26/2013 to 5/31/2019. Participants
must attain a score of 70% on each quiz to receive credit. Par-
ticipants receiving a failing grade on any exam will be notified
and permitted to take one re-examination. Participants will
receive an annual report documenting their accumulated
credits, and are urged to contact their own state registry
boards for special CE requirements.
24
24 COMPENDIUM EBOOK SERIES
COMPENDIUM EBOOK SERIES
March 2020 | Volume x Number x
April 2020 | Volume x Number x
2 Hours CE Credit
6. A rapid onset of analgesic activity is
desirable because it:
A. enhances patient comfort and reduces the
chance of excessive drug dosing.
B. increases the drug’s half-life.
C. reduces the chance of developing a
dependency.
D. eliminates any chance of comorbidity.
7. The most common adverse event
experienced by participants in this study was:
A. nausea.
B. a burning or stinging feeling of the nasal
mucosa immediately after dosing.
C. hives and itching.
D. an upset stomach.
8. Which class of drugs should represent the
first line drugs for most types of postsurgical
dental pain because of proven efficacy and a
favorable side-effect profile?
A. opioids
B. aspirin
C. non-steroidal anti-inflammatory drugs
(NSAIDs)
D. acetaminophen
9. Because of ketorolac’s high ulcerogenic
potential, intranasal ketorolac should not be
used for more than:
A. 2 doses.
B. 2 days.
C. 5 doses.
D. 5 days.
10. Weaknesses of this study were:
A. its open-label design.
B. that it lacked a placebo control and an
active comparator drug.
C. that it was not powered to determine
differences between the sites of implant
placement and the number of implants
placed.
D. all of the above
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