Pre-Emptive Analgesia in Dental Implant Surgery

Dental practitioners often prescribe opioids for the relief of moderate - severe acute
post-operative pain.1 There is evidence that alternative approaches, such as the use of long
acting local anesthetics along with the combination of non-opioid analgesics such as
acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), may prevent the need for
opioid medications. With the current national opioid overdose epidemic, government officials
have introduced new prescribing recommendations for the management of acute pain. Dentists
can play a role to address this epidemic by wider recognition and adoption of the new
prescribing recommendations for fast acting pre-emptive non-opioid analgesics to prevent
acute dental pain.2 Dentists are the fifth leading prescribers of opioids among health care
professionals accounting for 12% of the total immediate-release opioids prescribed in the
United States (U.S).3 With the increasing trends of opioid prescribing for dental surgeries
in the past few decades, dental implant procedures hold the highest increasing rate for
opioid prescribing.4 In the U.S alone, there has been as many as 183,000 prescription opioid
overdose related deaths from 1999 to 2015. Since 1999, the mortality rate from opioid
overdose has more than quadrupled.5 With more than 650,000 opioid prescriptions being
dispensed daily in the U.S,6 there has been a national call to alter the current prescribing
patterns of opioids to ensure appropriate indications and patient selection.7 There are
multiple adverse effects that may develop from opioid pain medications: nausea, vomiting,
constipation, dizziness, headache.8 However, two major concerns associated with the excessive
prescribing of opioids are overdosing leading to life threatening respiratory depression
problems and the creation of an environment that fosters the development of opioid
dependency, abuse and addiction.8 The U.S. Senate passed the 'Comprehensive Addiction and
Recovery Act' of 2016 to combat the opioid epidemic.9 This legislation is designed to prevent
opioid-related morbidity and misuse via physician and patient education, risk awareness,
proper prescribing practices, and efforts to improve safer handling of prescription opioids.9
NSAIDs are widely used for their anti-inflammatory, pain and fever reducing properties. In
the periphery, these drugs interfere with the formation of pro-inflammatory modulating
prostaglandins and thromboxane A2 via reversible inhibition of the cyclooxygenase enzymes
(Cox-1 and Cox-2). NSAIDs exact their effects through a variety of peripheral and central
mechanisms. Their efficacy in the reduction of post-operative pain has been widely
documented.10 It has been demonstrated that a single dose of an NSAID (i.e. etoricoxib,
ketoprofen, diclofenac potassium, diflunisan, ibuprofen) may provide better acute
post-operative analgesia than some commonly prescribed single dose opioids, even when they
are prescribed in combination with other NSAIDs.10 There is also sound evidence that some
individuals receive synergistic analgesic effects when NSAIDs are combined with
acetaminophen.11 However, these effects can vary, as not everyone will achieve adequate pain
relief even from the most potent drugs. Simple drug combinations of fast acting
anti-inflammatories with acetaminophen can reliably provide successful analgesia for many
acute pain patients in reasonably low doses.10 While modern dental literature contains
numerous articles that support the tolerability, safety and efficacy of NSAIDs, many dental
practices continue to prescribe opioids in cases which would likely respond better to other
analgesics. Many dentists still underrate the risks and abuse of opioids. That is why it is
important to design and test more lucid protocols for prescribing analgesics in dental care
settings.

Severity of post-operative pain in periodontal and dental implant surgery can vary between
mild to severe 12,13 and patient-reported outcome measures (PROMs) can be adverse at times.14
There is evidence that straightforward implant placement procedure is a surgical procedure
associated with relatively low postoperative pain and pain management following dental
implants is usually achieved by the use of drugs such as NSAIDs, acetaminophen, and/or
opioids.11,15 Pre-emptive analgesia refers to the reduction of pain severity that occurs
post-operatively by suppressing pain pre-emptively prior to the performance of the surgical
procedure.16,17 Previous studies have shown the rationale and efficacy of using pre-emptive
analgesia in periodontal and oral surgical models.18-25 Long acting local anesthetics such as
bupivacaine have been shown to prolong the onset of and suppress postoperative pain better
than lidocaine, an intermediate duration anesthetic.26,27 With successful pre-emptive
analgesia including NSAIDs and long acting local anesthetics, the need for stronger
post-operative analgesics, like opioids, may be significantly decreased.

Inclusion Criteria:

- Adult patients 18 years of age and under 65 years of age

- ASA Type I & II

- Single tooth edentulous site requiring dental implant placement without any additional
bone or soft tissue augmentation at the time of implant placement

- Patients not requiring use of any form of sedation for dental implant surgery
(nitrous, oral or IV sedation)

Exclusion Criteria:

- Hypersensitivity to NSAIDs, salicylates, or microcrystalline cellulose NF (Avicel PH
105)

- Liver disease

- Renal disease

- Hypertension and taking angiotensin-converting-enzyme inhibitors and/or diuretics

- Significant respiratory conditions including acute or severe asthma.

- Cardiovascular disease that will prevent the patient from going through the surgical
procedure or consuming the required medications: cardiac disease, cardiomyopathy,
cardiac arrhythmias, coronary heart disease, acute MI, angina, history of MI, coronary
artery bypass grafting (CABG), Aspirin intake, peripheral vascular disease, cerebral
vascular disease (stroke, TIA)

- Gastrointestinal disease including irritable bowel disease and gastric ulcers

- Hematological diseases (coagulopathy, hemophilia or thrombocytopenia)

- Pregnancy/lactation at the time of surgery

- Heavy smoking (>10 cigarettes per day)

- Diabetes

- Allergies or intolerance to ibuprofen, opioids, and local anesthetic (lidocaine and
bupivacaine)

- History of recreational drug abuse

- History of heavy alcohol use. Substance Abuse and Mental Health Services
Administration (SAMSHA)30 defines heavy alcohol use as binge drinking on 5 or more
days in the past month. SAMSHA defines binge drinking as 5 or more alcoholic drinks
for males or 4 or more alcoholic drinks for females on the same occasion (i.e., at the
same time or within a couple of hours of each other) on at least 1 day in the past
month.

- Patients currently taking prescription pain medications or have taken over-the-counter
pain medications within 4 days of surgery.

- Patients with drug-drug or drug-disease state interactions

- Other significant medical conditions (not reported above) that are likely to prevent
the patient from going through the surgical procedure or consuming the required
medications.